Ambulatory Intravenous Inotropic Support in Pediatric and ... · •14 pts on home IV milrinone and/or dobutamine, age 6-18 yrs - Duration 14-476 (median 68) days - 8 palliative care,

Ambulatory Intravenous InotropicSupport in Pediatric and Congenital

Heart Failure: How to Evaluate Outcomes

Sotiria Apostolopoulou

Department of Paediatric Cardiology and Adult Congenital Heart Disease

Onassis Cardiac Surgery Centre, Athens, Greece

Background

• CHD and CM cause end-stage HF in children and adults CHD patients

frequently requiring inotropes and MCS as a bridge to transplant in up

to 57% of cases

• Children on MCS, even for a short time, have:

- survival rates to transplant or recovery as low as 75%

- risk for thromboembolic, hemorrhagic, neurologic events, respiratory

failure and multisystem organ failure

• In the absence of heart transplantation, end-stage HF has significant

morbidity and mortality, poor quality of life, complicated management,

and frequently, long-term continuous inotropic support in the ICU

• Post myocarditis dilated CM, even if needing inotropic or MCS, has a

significant chance of recovery within 2 years → should these patients

receive long-term inotropic support prior to referral for transplant?

Ambulatory inotropic therapy in end-stage HF in adults

• AI therapy is advocated in stage D HF for 1) pts awaiting heart

transplant or MCS or 2) palliative care in non eligible pts

• Older studies showed that home inotropic therapy in adults, despite

improving clinical status and lowering cost, increases mortality and

morbidity probably related to arrhythmic events•

• Low dose PO enoximone is safe but does not improve mortality,

cardiovascular hospitalization or 6MWTD

• 112 inotrope dependent pts (not transplant candidates)

- median F/U: 130 days (2-2345 days)

- High mortality (76%), rehospitalization 49%

• Trend towards MCS with the significant risks of thromboembolic

events, bleeding, cerebral hemorrhage, pump malfunction, etc

ACCF/AHA guideline for the management of heart failure JACC 2013

ESSENTIAL trials. Metra et al. Eur Heart J 2009

Gorodeski et al. Circ Heart Fail 2009

Packer et al. N Engl J Med 1991

Hampton et al. Lancet 1997

Cohn et al. N Engl J Med 1998

Park et al. Circ Heart Fail 2012

Experience with ambulatory inotropic therapy in children with end-stage HF

• 14 pts on home IV milrinone and/or dobutamine, age 6-18 yrs

- Duration 14-476 (median 68) days

- 8 palliative care, 6 awaiting heart transplant

- Safe, cost, family dynamics with hospitalization

• 7 pts on home IV inotropes, age 14.6 ±3.7 yrs

- Duration 4-84 (median10) wks

- 1 death, 5 complications in 2 pts, 6 pts bridged to transplant

- EF from 30 to 39% on therapy

• 106 pts on home IV inotropes, age 10.1±6.4yrs

- Duration median 47 days (4–323 days)

- 85% transplant

- 8% weaned from support

- 6% deaths

Berg et al. J Heart Lung Transplant 2007

Price et al. J Card Fail 2006

Birnbaum et al. Circ Heart Fail 2015

Criteria for IV ambulatory inotropes (AI) and/or Levosimendan (LS)

• Intractable CHF despite maximum oral therapy

• Cause: myocarditis, dilated CM, restrictive CM, CHD

• Inability to wean IV inotropes after multiple attempts of slow weans over at least 4 weeks

• Stabilization on IV inotropes without need for ICU

• Without significant arrhythmia–Defibrillator if indicated

• Local Transplant Team → negative for mechanical assist device, mostly due to age and size

Apostolopoulou SC, et al. Pediatr Cardiol. 2018 Oct;39(7):1315-1322

Protocol for ambulatory inotropes

• Maximal tolerated oral therapy, including β-blockers, diuretics

and ACE inhibitors along with the IV inotropes

• Subsequent initiation of levosimendan infusions q 2-3 wks

• Stable in hospital for at least 4 weeks

• Insertion of central Hickman catheter

• Education of 2 caretakers (incl. the pt if >12 yo) in sterile

procedures, infusion preparation, pump function etc

• Patients stay locally for 2 additional weeks

• Periodic attempt at slow wean of inotropes


Population Demographics

Characteristics No (%)

Patients 27

Gender

Male 16 (59%)

Female 11 (41%)

Age at initiation of therapy 9.4 (0.1-26.1) years

NYHA Class at initiation of therapy III-IV

NT- proBNP at initiation of therapy 2542 (320-16166) pg/ml

Inotropic therapy

Ambulatory Inotropes alone 7 (26%)

Levosimendan alone 6 (22%)

Combined Ambulatory Inotropes and Levosimendan 14 (52%)


Diagnosis No (%)

Myocarditis 6 (22%)

Dilated cardiomyopathy 13 (48%)

Restrictive cardiomyopathy 2 (8%)

Postoperative CHD 6 (22%)

Single ventricle s/p Fontan 1

Single ventricle s/p Glenn 1

Aortic stenosis s/p Ross operation 1

Anomalous LCA origin from PA s/p reimplantation 1

CCTGA s/p tricuspid valve replacement 1

CAVC s/p biventricular repair and mitral valve replacement 1

Diagnoses


Diagnosis –Age at initiation

0

2

4

6

8

10

12

14

Myocarditis Dilated CM Restrictive CM CHD

Diagnoses

22%

48%

8%

22%

Nu

mb

er o

f p

atie

nts

0

2

4

6

8

10

12

0-1yo 1-5yo 5-10yo 10-18yo >18yo

Age at initiation of AI/LS

Nu

mb

er o

f p

atie

nts

22%

15%

37%

7%

19%


Results – Summary (27 pts)

• Median F/U 2.1 (0.3-21.3) years

• 4 pts (2 DCM, 2 RCM): prolonged hospitalization and death after 0.8-2.1 years (mortality 15%)

• 6 pts (22%): heart transplantation after 0.3-2.3 years

• 17 pts stable for 4mos to 3.4 yrs

• WHO class I-II, good QoL, good social life, attending school, playground

• AI weaned and discontinued in- 6 improved myocarditis pts after 1.2 (0.4-2.3) yrs - 2 CM pts after 0.7 and 3.7 years (still on LS infusions)- 1 CM pt with LVAD and was transplanted 3.5 yrs later


AI as bridge to recovery

• 6 patients

• 3 Parvo B19

• 4 pts received:

- AI for 0.3-1.3 yrs

- LS for 0.3-1.2 yrs

• 2 pts received:

- only LS for 1.1-2.3 yrs

• Post discontinuation:

stable without HF or

deterioration and LVEF >

60% over 2.8 (0.6-3.4) yrs0 5 10 15 20 25

6

5

4

3

2

1

AI

LS

Bridge to recovery

Pat

ien

ts

Months


AI and/or LS as bridge to recovery

1 mo after discontinuation of HI,

SF 33%

Initial SF 16% 9 mos HI, SF 26%

2.7 yrs after discontinuation of HI,

SF 40%

6 mos HI, SF 14%

1 yr after discontinuation of HI,

SF 33%


Home inotropes as bridge to recovery

SF (%) versus time (months)

0

10

20

30

40

50

0m 3m 6m 12m 24m 30m

25

35

45

55

0m 3m 6m 12m 24m 30m

LVEDD (mm) versus time (mos)

• 3 parvovirus myocarditis patients with full recovery

• All needed both IV inotropes and levosimendan initially

• One agent discontinued after months, but remodeling and recovery

required treatment for 1 year

=Stop inotropes

=Stop levosimendan

SF (%)LVEDD


AI and/or LS as mainstay therapy

• 4 deaths after 0.8-2.1 years of AI

• 11 pts stable WHO class II: 7 pts AI+LS for 0.3-3.7 yrs / 4 pts only LS for 0.5-4.2yrs

• 3 discontinuations (1 LVAD, 2 CM still on LS)

0 5 10 15 20 25 30 35 40 45 50

15

14

13

12

11

10

9

8

7

6

5

4

3

2

1

AI LS

Mainstay therapy

: deaths

Pat

ien

ts

Months


AI and/or LS as mainstay therapy

2 yrs home inotropes

LVEDD 45mm, SF 21%, 2+ MR

3.4 yrs on HI, monthly Simdax

LVEDD 47mm, SF 21%, 2+ MR

Attempt at weaning

Start inotropes in hospital, home

after 1 month

LVEDD 48mm, SF 18%, 3-4+MR

AI and/or LS until Transplant

• 6 patients, dilated CM, AI 3-27 mos, levosimendan 7-24 mos

• Pts 1,2: heart transplant on AI (F/U 21 years post transplant)

• Pt 3: abrupt stop inotropes→shock→LVAD→Heart Tx (F/U 2 yrs)

• Pt 4, 5, 6: abrupt stop inotropes→shock→ECMO→Death

0 5 10 15 20 25 30

6

5

4

3

2

1

AI LS

Bridge to transplant

*

*

*

: deaths

Months

Pat

ien

ts


AI in PH due to LV dysfunction

44

62

28 28

1.6 1.7

9.8

19.8

32

26

20

14

3.6 3 2.84

0

10

20

30

40

50

60

Pt 1 Pt 2 Pt 1 Pt 2 Pt 1 Pt 2 Pt 1 Pt 2

Mean PAP(mmHg) PCWP(mmHg) CI (L/min/m2) PVRI (Wood U)

Baseline

After AI

Pulmonary hypertension in HF

Hem

od

ynam

icva

riab

les

bef

ore

an

d a

fter

AI

Both patients underwent successful heart transplantation at our

institution and remain stable over 21 years follow up


Ambulatory inotropes - Quality of life

• Diagnosis DCM 2.9yo

• Stabilization only on IV

Dob/Mil at 3.1 yo

• AI for 3.7 yrs

• Monthly LS 3.9 yrs

• Now 8yo

• 3rd grade at school

• Happy, playful with 4yo

brother

• Successful weaning of AI last

year, remained on LS, she

went swimming last summer!

Complications - Safety

• 4 line infections, in 3 patients:- 3 → IV antibiotics for 2 weeks with subsequent negative

cultures for weeks- 1 → 2nd infection 6 mos after the 1st → inadequate response to

IV antibiotics → catheter removal and reinsertion later

• 4 catheter dislodgements in infants → reinsertion

• No reports of pump malfunction or emergent hospital admissions apart from the line infections

• No neurologic, bleeding or thromboembolic events

• No sudden deaths, no defibrillator discharge


Heart or Heart-Lung Transplantation

• No pediatric heart transplant program in Greece

• Adult heart transplant program in Greece considers patients > 12 yo or small adult size

• Donor shortage (6-10 per year for Greece)

• No heart-lung or lung transplant program in Greece (for pulmonary hypertension pts)

• Difficult acceptance of candidates in foreign programs

• CHD issues: prior operations, guarded results, difficult acceptance of candidates in foreign transplant programs


Conclusions-Long-term AI and/or LS

• Feasible, safe, with few complications in pediatric pts with intractable CHF, even in infants

• Good QoL considering severity of disease

• Mainstay therapy in absence of transplant option

• No sudden deaths or significant arrhythmias (nonischemicetiology)

• Allows remodeling and possible recovery in myocarditis, which may take up to 1 year

• Improves PH to allow possible heart transplant

• Provides time to allow transfer in foreign Pediatric Transplant Program or allow growth to permit transplant in local Adult Transplant Program


There is no conflict of interest

Documents

Ambulatory Intravenous Inotropic Support in Pediatric and ... · •14 pts on home IV milrinone and/or dobutamine, age 6-18 yrs - Duration 14-476 (median 68) days - 8 palliative care,