Download PERIPARTUM CARDIOMYOPATHY

Pregnancy and the
Heart (and Vessels)
Jorge Cheirif, MD, FACC, FASE
Outline
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Thrombosis
Valvular heart disease
HTN
Pregnancy related CMP
Thromboses during Pregnancy
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Leading cause of maternal mortality.
Levels of AT III, protein C and S fall throughout
pregnancy. F VIII, IX, XI increase in pregnancy
Prior DVT, emergency C section.
AT III deficiency associated with 2-4 fold higher
risk (14%) than PC or PS.
F V Leiden (PC resistance) and F II 20210A
(inhibits fibrinolysis) combo increases risk of DVT.
Heterozygous 4% risk. If Hx DVT and both
factors present, 50% risk.
AT deficiency and FV Leiden worse post-partum.
Risk 41% homozygous,9.2% double homozygous
Risk Stratification
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Predictive role of prior Hx DVT
Age >35
Obesity
Varicose veins
Protein deficiencies. APLA
Dx of DVT
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DVT 1-2/1000 pregnancies.
Difficult to Dx, especially if pelvic
veins are involved.
Compression US: If + treat (occas
false +). If –ve, and still suspect DVT
Venous duplex, impedance plethysmography, venography or MRI, V/Q.
In APL Syndrome, heparin/LMWH +
ASA
Thromboses Management
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Heparin: Osteopenia, HIT.
LMWH: Better tolerated than UFH,
safe, ? Prosthetic heart valves
effectiveness. No epidural.
Coumadin: crosses placenta.
teratogenic (OK 2-3 trimester),
bleeding if not stopped 2-3 weeks
prior to delivery.
Outline
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Thrombosis
Valvular heart disease
HTN
Pregnancy related CMP
CV System and Pregnancy
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Increase up to 40-50% plasma volume
Relative anemia
Increases in CO (HR increases, SVR and PVR decrease,
therefore wide PP)
IVC obstruction (supine) abrupt decrease CO.
In labor increase in CO 60-80%. Post delivery increases in
preload
CV complications (13%): poor FC, LVOT obstruction (>30
mmHg), EF <40%, cyanosis, prior events or arrhythmias.
Risk 27% with 1 risk factor, 70% with >2.
Neonatal complications (20%): FC, cyanosis, LVOT
obstruction, anticoagulation, smoking, multiple prior
pregnancies.
Physical Exam
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Faster HR (10-20 beats), bounding
pulses, widened PP, low N SBP, warm
extremities.
High normal JVP. Thyroid may be
enlarged. S2 widely split. S3 is
common. I-II/VI SEM LUSB. Continuous murmur. Diastolic M unusual.
MS or AS M increase, AI or MR less.
VHD associated with low Maternal
and Fetal Risk
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Asymptomatic AS with low mg (<50)
with normal EF.
NYHA FC I or II AI with N EF.
NYHA FC I or II MR with N EF.
MVP with no MR or mild to mod MR
and N EF
Mild to mod MS (MVA >1.5 cm2, mg
5 mmHg) without pulmonary HTN.
Mild to moderate PV stenosis
VHD lesions associated with high
Maternal and/or Fetal Risk
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Severe AS with or without symptoms
AI with NYHA FC III-IV.
MS with NYHA FC II-IV.
MR with NYHA FC III-IV.
AVD or MVD with severe pulm HTN.
AVD or MVD with EF< 40%.
Mechanical prosthesis.
AI in Marfan Syndrome
CV System and Pregnancy
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Regurgitant lesions are well tolerated
Stenotic lesions increase morbidity of
mother and fetus. Higher incidence of CHF,
arrhythmias, hospitalizations pre-term
delivery, low birth weight.
Correct, if possible VHD prior to
conception.
In MS: BB, diuretics, anticoagulation, PBV
if severe SXS.
In AS: Rx CHF, if severe PBV or AVR.
Prosthetic Mechanical Valves
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Discontinue warfarin as soon as Dx
of pregnancy is established.
Start heparin (or if lawyers do not
scare you, LMWH), S/Q to prolong
PTT to therapeutic range.
Replace heparin with warfarin (INR
2.5-3.5) at week 12 and continue to
middle of 3rd trimester, then restart
heparin.
UNsafe drugs during Pregnancy
Drug
Warfarin
Amiodarone
Nitroprusside
ACE-I
Diuretics
Effects
Fetal hemorrhage embryopathy,
CNS abnormalities
IUGR, prematurity,
hypothyroidism
Thiocyanate toxicity, fetal loss
Skull ossification defect, IUGR,
PDA, LBW, ATN, anemia, death
Placental hypo-perfusion, low
platelets, jaundice, low Na+ & HR
Outline
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Thrombosis
Valvular heart disease
HTN
Pregnancy related CMP
HTN in Pregnancy
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2nd leading cause of maternal
mortality (15% deaths).
HTN disorders 6-8% pregnancies.
Contributes to still-births and neonatal morbidity and mortality.
Abruptio placenta, DIC, cerebral
hemorrhage, hepatic failure, ATN.
Etiology unknown.
Risk of CHF, encephalopathy PP.
Classification of HTN
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Chronic HTN (>140/90 mmHg).
Pre-eclampsia-eclampsia (>20 wks).
Pre-eclampsia superimposed upon
chronic HTN.
Gestational HTN (<20 weeks):
- Transient, if no pre-eclampsia. BP
returns to normal by 12 weeks
- Chronic HTN if it persists.
Pre-eclampsia
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Proteinuria: > 0.3 g protein in 24 hr. Correlates 1+ dipstick
or 30 mg/dL.
SBP >160 or DBP >110 mmHg.
Proteinuria >2g/day (1st time).
Increase serum creatinine (>1.2)
Platelet ct <100K and/or micro-angiopathic anemia (high
LDH).
High liver enzymes
Persistent headache or cerebral/visual abnormalities.
Persistent epigastric pain.
Eclampsia= seizures in pre-eclampsia.
Edema no longer a criteria.
Pre-eclampsia
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Can progress slowly or very fast (hrs).
Maternal: vasospasm, activation of
coagulation system, perturbation in
volume and BP control (sensitive AII, loss
circadian rhythm). Oxidative stress and
inflammatory-like responses.
Pathologic changes ischemic and affect
placenta, brain, kidney, liver.
Pre-eclampsia
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Renal lesion: glomeruli are swollen due to
hypertrophy of endothelial and mesangial
cells which encroach the capillaries
(“glomerular endotheliosis”). Decrease
25% GFR and RBF, however since renal
function increases 35-50% in pregnancy, a
normal creatinine does not exclude preeclampsia. ATN. Hyperuricemia. Low
calciuria. Low intra-vascular volume.
Pre-eclampsia
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Thrombocytopenia (<100K) rarely
severe. Cause unknown (deposit at
sites of endothelial damage and/or
immunologic process). Fetuses born
show no problems.
Liver: range from mild necrosis to
ominous HELLP syndrome (hemolysis
elevated enzymes, hepatic bleeding
or rupture.
Pre-eclampsia
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CNS: Headache, visual disturbance
(blurred vision, scotomata, cortical
blindness), focal signs. Seizures
(eclampsia) due to coagulopathy and/or
HTN encephalopathy.
High risk for it: in pts with Hx HTN,
previous gestation, multiparous, DM CVD,
renal vascular or parenchymal disease,
multi-fetal pregnancy.
Sonogram to evaluate fetal growth 25-28
weeks.
Pre-eclampsia superimposed on
Chronic HTN
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Much worse prognosis.
HTN without proteinuria <20 weeks.
Sudden increase in proteinuria.
Sudden increase in BP, previously
under control.
Thrombocytopenia (<100K).
Increase in LFT’s.
Gestational HTN
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HTN first Dx in mid pregnancy.
No proteinuria.
BP returns to N by 12 weeks PP. If it
persists, chronic HTN.
Pregnancy Counseling
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If HTN severe prior to pregnancy
(180/110) evaluate for 2ary causes. Stop
ACE-I. If target organ damage (creatinine
>1.4), advise higher risk for fetus (loss 10
fold), may also exacerbate HTN if
pregnancy occurs.
No wt loss. Na restriction (2.4 g).
Alcohol aggravates HTN. Tobacco risk
placental abruption and fetal growth
restriction.
Treatment HTN
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Mild chronic HTN does not need Rx during
pregnancy. Rx if >150/100 persists. Methyldopa
preferred (N placental flow and F/U in kids up to
7 years. Labetalol good alternative. Limited data
Nifedipine SR OK. Hydralazine.
Diuretics: effective. Theoretical risk.
ACE-I contraindicated.
All anti-HTN can appear in breast milk.
Methyldopa and hydralazine OK. Labetalol and
propranolol OK. ?CaB. Diuretics may suppress
lactation. No ACE-I.
No proven value of low dose ASA for most, of Ca
Mg, fish oil. Vit C and E, encouraging results.
Pre-eclampsia Rx
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Vaginal delivery preferred.
MgS04 for seizures.
Acute HTN: Hydralazine (IV or IM) 5 mg
bolus 1-2 min, subsequent doses in 20
min. Labetalol IV 20-40 mg bolus, then 1
mg/Kg infusion. Nifedipine used, but not
approved, careful when Mg used.
Recurrence rate (particularly if < week 30)
up to 40% (higher if multiparous)
subsequent pregnancies, if HELLP, 5%.
Outline
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Thrombosis
Valvular heart disease
HTN
Pregnancy related CMP
As a Cardiologist, I worry when:
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90% of the reports of PPCMP are
published in non-cardiology journals.
Tremendous variability in definitions,
response to treatment and outcomes
in various reports.
No controlled randomized studies.
The NIH decides to hold a “panel of
experts” to shed light on a “rare and
catastrophic disease”
NIH Expert Panels
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Meetings in Bethesda.
Attempts to reach “consensus”. After
all, they are supporting the meeting:
Reimbursement for:
• meals/day: $25. Marriot’s breakfast:
19.90+7= $26.90
• Hotel: $100. Actual cost: $187
• Airfare: $495. Actual cost: $980
ABILITY TO IMPRESS YOUR GRANDMA:..PRICELESS
Perspective
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4.6 million people Rx for CHF.
550,000 new annual cases.
1 and 5 year survival rates 76/35%.
Numerous clinical (older age, NYHA,
LVEF, RVEF), biochemical (NE, BNP),
EPS (VT, AF) and hemodynamic
variables (MVO2) influence survival.
Underlying ischemia (59 Vs 69%) 5
yr survival.
Perspective (cont.)
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HIV and amyloid related CHF have
high mortality.
Inflammatory cytokines and
oxidative stress potential mediators.
Gouley first described PPCMP in
1937.
Spectrum of DCMP
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At least 75 specific diseases of heart
muscle.
However, Rx, Px utility of identifying
them is unknown.
1,278 pts with DCMP (’82-’98) at JH.
Endomyocardial biopsy in all (0.2%
mortality), and cath, if risk factors
present. 50% cases idiopathic.
Felker M. Medicine 1999;78:270
Spectrum of DCMP
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50% of PPCMP pts showed evidence of
myocarditis. (previous pathologic studies
also found evidence of it).
Resolution of myocarditis, with or without
immunosupression correlates with
improved function. Rx only if seen shortly
after SXS onset, and if no spontaneous
recovery.
Anticoagulation unless contraindicated.
Felker M. Medicine 1999;78:270
Causes of DCMP and Survival
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1230 pts. (1982-1997) with CHF
underwent Bx for unexplained CMP.
RHC (and LHC if CAD suspected).
Idiopathic, peripartum, CAD, HTN,
HIV, infiltrative, myocarditis,
substance abuse, CTD, doxorubicin.
614/1230 specific cause, rest
idiopathic. Bx specific Dx 15%.
Complication 8%, 0.2% mortality.
Felker GM. NEJM 342;15:1077
Causes of DCMP and Survival
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F/U 4.4 yrs 417 pts died, 57 underwent
transplantation.
In comparison to idiopathic DCMP, PP
better Px (5 yr survival of 94%,HR 0.14,
p<.001), worse for infiltrative (4.79,
p<.001), HIV (4 p<.001), doxorubicin
(2.64, p.005), IHD (2.01, p<.001). Same
for HTN, myocarditis, substance abuse,
CTD.
26/51 with PPCMP had myocarditis by Bx.
NIH Workshop
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April ’97, Cardio, OB, Immunologists
and Pathologists.
Definition:
• CHF 1 month pre-delivery & 5 months
after.
• Absence of identifiable cause.
• Absence of prior recognizable HD.
• LV systolic dysfunction.
Pearson G. JAMA 2000;283:1183
NIH Workshop
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Risk factors: multiparity, advanced
maternal age, pre-eclampsia, gestational HTN, African American.
Etiology: myocarditis, abnormal
immune response to pregnancy,
hemodynamic stress, stressactivated cytokines, prolonged
tocolysis. ? Familial CMP.
NIH Workshop
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Myocarditis: Reported from a few cases to 76%
(Bx ASAP and borderline criteria). Time between
SXS and Bx, histologic criteria. Pregnant mice
susceptible to viruses
Abnormal immune response: occurrence of
chimerism of the hematopoietic lineage cells from
the fetus to the mother.
What the h___ is that?
Fetal cells pass into the maternal circulation,
colonize the heart and remain without being
rejected ‘till immunogenicity returns.
Serum levels of Antibodies
Antibody titers
Group
<1:20
1:20-1:160
ANT
>1:160
DCMP
16/56
29/56
11/56
PPCMP
1/10
1/10
8/10
BCKD
DCMP
PPCMP
30/56
0/10
21/56
2/10
Myosin
DCMP
PPCMP
18/56
1/10
27/56
1/10
5/56
8/10
11/56
8/10
Definition and Epidemiology
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Unexplained LV failure in the last
month of pregnancy or within 5
months post partum.
Incidence: 1 in 1500 to 1 in 15,000.
Early studies, mortality rates 2550%, half of them in first 3 months.
10% of them with myocarditis at Bx.
Immunosuppressive Rx helpful?
Etiology
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Unknown. However, some interesting
findings:
• Incidence: 1/15000-1/1300 USA and 1% in
Nigeria. Blacks, twin pregnancies, toxemia,
post-partum HTN.
• Prolactin: HTN and cardiomegaly seen in 1/5
cases of prolactinoma; increases throughout
pregnancy. Receptors on B and T lymphocytes
and NK cells. Requires selenium for action.
Low levels of selenium in Africa and some
areas of China where PPCMP is common.
PATHOGENESIS
Genetic Factors
Twin Pregnancy
Stress
Micro adenoma
Cocaine
Prolactin
Selenium deficiency
Decidual prolactin
Lymphoblastoid prolactin
Viral infection
Toxemia
HTN
Auto immunity
Ventricular dysfunction
Modified from Kothari S. IJC 1997;60:111
Diagnosis and Management
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Symptoms and signs of CHF, new
murmurs.
Exclusion of other causes of CMP.
Diuretics, hydralazine, digoxin; ACE only
post-partum and if not breast feeding.
BB not contraindicated in pregnancy.
Heparin before delivery, then Coumadin.
?IV gamma globulin.
Heart transplant if failure with all else.
To Bx or not to Bx
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Confirm the presence of myocardial
infiltration (amyloid, hemochrom),
myocarditis, transplant rejection.
Non specific findings (hypertrophy,
fibrosis, necrosis) and sampling.
Presence or absence of myocarditis
results in similar mortality (fulminant
in young people?).
Alters medical management?
Clinical and Therapeutic Aspects
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Multiparity, twin births, advanced
maternal age, pre-eclampsia,
gestational HTN, AA.
About 50% recover completely.
Persistence of CMP > 6 months =
poor prognosis.
Risk for recurrence is high in
subsequent pregnancies.
Mehta NJ. Angiology 2001;52:759
Maternal and Fetal Outcomes post
PPCMP
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Retrospective study of 44 women with 60
subsequent pregnancies. Gp 1 (n=28) had
normal LVEF. Gp 2 (n=16) abnormal.
Mean age 29. Dx pre-delivery in 7, 1st
month post in 28, 2-6 months in 9. 10 had
pre-eclampsia, 4 HTN. 3/7 had +
myocarditis on Bx.
Subsequent pregnancy (1 in 33, 2 in 6, 3
in 5) 27 months, F/U 90
Elkayam U. NEJM 344;21:1567
Maternal and Fetal Outcomes post
PPCMP
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6/28 pts in Gp 1, and 7/16 in Gp 2 had
CHF in subsequent pregnancy.
21 and 25% respectively had a > 20 % EF
drop, and 14 and 31%, respectively had a
decreased EF at last F/U.
None of Gp 1 pts died. 3 of Gp 2 died after
subsequent pregnancy.
In 9 women abortions induced, had < EF
(46 to 43 Vs. 49 to 42)
Premature delivery in 3 Gp 1 and 6 Gp 2.
No fetal death.
Elkayam U. NEJM 344;21:1567
MEAN EF IN PPCMP
60
Percent of women
50
40
All women
Group 1
Group 2
30
20
10
0
Index
Postpartum
Subsequent
Last F/U
Elkayam U. NEJM 344;21:1567
Prognosis
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Depends on normalization of LV
function. Demakis, half of 27 women
had persistent dysfunction and
mortality was 85%. In the ones that
recovered, no mortality. Sutton, 6/14
pts with no recovery died. Survivors
had higher EF (23 vs. 11).
Better to be rich and healthy than
sick and poor!!!
Prognosis
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21 pts with PPCMP (’85-93). 18 with serial
echo F/U. After baseline echo, dobutamine
and methoxamine used to determine
contractile reserve. 7/10 with reserve
improved, none without. Matched controls.
Increased intravascular volume, cardiac
output and HR and lower SVR
Contractility normally remains unaltered
during pregnancy.
Lampert M. AJOBGYN 1997;176:189
Contractile Reserve (D Vcfc in circ/sec)
Prognosis Assessment
1.2
Dobutamine
1
0.8
0.6
0.4
0.2
0
0
20
30
40
50
60
70
Hemodynamics in PPCMP
40
% Change
30
20
10
Recovered
Control
0
-10
-20
-30
HR
CO
PVR
Prognosis
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28 women; 8 SXS ante-partum; 20 postpartum. 19 with pre-eclampsia or HTN Hx.
13 premature deliveries. Perinatal
mortality: 36/1000 births.
ECG: LVH (14), NSSTT (7).
1 recovered completely; 2 died early, 3 in
follow up, 3 required transplant and 18
had stabilization of symptoms.
6 had subsequent pregnancies, and 4 had
relapses of their PPCMP.
Other reports, 50% have good prognosis.
Witlin A. AJOBGYN 1997;176:182.
War Time Joke
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During a French-British war, a French
officer asked a British one: How
come you guys wear red coats? It
makes it so easy to identify you!!!
The British answered, we do it so
that if we get injured, our soldiers
will not see us bleed and panic.
Since then, the French were brown
pants.
Effect of New Pregnancies
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44 pts with Hx PPCMP. Nine pregnant
again. Two lost F/U.
All 7 tolerated pregnancy relatively
well and delivered healthy babies.
4 pts with FC II, and 2 with III, no
change. One from III to II.
EDD was same (61 to 58 mm), ESD
(50 to 47 mm, p=.008), FS (19 to
23%).
De Souza JL J Card Fail 2001;7:30
Course of Subsequent Pregnancy
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34 pts (mean 26 yrs).
5 in FC II, 1 in FC III, 28 in FC IV.
All advised against new pregnancies.
12 (35.3%) became pregnant. 6 (Gp 1)
had normal heart size, 6 had persistent
cardiomegaly (Gp 2).
5/6 in Gp 1 did well pre- post- pregnancy.
All Gp 2 tolerated pregnancy well,
however 2/6 deteriorated and died 8 & 13
years after.
3 year interval post recovery LVEF safe.
Filho A. Arq Bras Cardiol 1999;73:47
Summary
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Outcome highly variable. Regardless of
initial severity, some pts clinical and echo
status improve rapidly, and others
deteriorate rapidly and need
transplantation or die. Others have
persistent dysfunction and over years
improve.
Hemodynamic stress of pregnancy can
unmask impaired reserve.
Anticoagulants, ACE. IABP in severe cases
Reimold SC. NEJM 2001; 344:1629
If worse comes to worse….would
transplant work?
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Case reports.
22 yo with multi-organ failure post
partum. CI 1.9 L/min, IABP, Novacor
LVAD. Bx severe non-inflammatory
lesions c/w DCMP. TIA’s, acute
abdomen: thrombosis SMA, bowel
resection ileostomy. 158 days later!!
Orthotopic heart transplant.
Tandler R. EJCT Surg 1997;11:394