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Case Report
Early Extracorporeal Membrane Oxygenation Support
for 5‑Fluorouracil‑induced Acute Heart Failure with
Cardiogenic Shock
Robert Höllriegel, Julia Fischer, Gerhard Schuler
Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center, Leipzig, Germany
ABSTRACT
A 50‑year‑old man with no previous history of cardiovascular disease or risk factors was admitted for syncope and orthopnea.
Importantly, he underwent recent chemotherapy with 5‑fluorouracil (5‑FU) until 1 day before his acute presentation. In the
emergency room, patient developed asystole and was successfully resuscitated for 2 min. At coronary angiography, no signs
of coronary artery disease were detectable, but transthoracic echocardiography showed a severely decreased left‑ventricular
systolic function. Due to the progressive cardiogenic shock, an extracorporeal membrane oxygenation (ECMO) support was
used as bridge-to-recovery and to avoid the use of sympathomimetics with their known disadvantages. On ECMO support,
hemodynamic stabilization was evident and medical heart failure treatment was commenced. Left‑ventricular function
recovered to normal values within a short period of time. Cardiac complications after chemotherapy with 5‑FU are not rare
and should be taken into consideration even in acute heart failure with cardiogenic shock. ECMO as the most potent form
of acute cardiorespiratory support enables complete relief of cardiac workload and therefore recovery of cardiac function.
Key words: Acute heart failure, cardiogenic shock, extracorporeal membrane oxygenation support, 5‑fluorouracil
How to cite this article: Höllriegel R, Fischer J, Schuler G. Early extracorporeal membrane oxygenation support for 5-fluorouracil-induced acute
heart failure with cardiogenic shock. Heart Views 2014;15:26-8.
© Gulf Heart Association 2014.
INTRODUCTION
5
‑fluorouracil (5‑FU) is a widely used
chemotherapeutic drug and cardiac complications
are not rare. [1] Angina is the most common
clinical presentation. However myocardial infarction,
Tako‑Tsubo‑like syndrome and cardiogenic shock are
also described.[1‑3]
CASE REPORT
A 50‑year‑old man (weight 70 kg, height 180 cm)
was admitted to a primary care hospital following an
episode of syncope. He reported acute orthopnea and
an attack of sweating at night accompanied by nausea
and vomiting before loss of consciousness for 1 min.
Angina pectoris was denied by patient.
In the emergency room, patient developed asystole
and was immediately and successfully resuscitated
for 2 min. Afterwards, he was fully oriented without
any neurological dysfunction. Consequently, he was
Address for correspondence: Dr. Robert Höllriegel,
Department of Internal Medicine/Cardiology, University of Leipzig - Heart Center,
Struempellstrasse 39, 04289 Leipzig, Germany.
E-mail: [email protected]
HEART VIEWS
Jan-Mar 14 Issue 1 / Vol 15
transferred to our heart center for further diagnostic
work‑up and therapy.
Importantly, patient had no previous history
of cardiovascular disease or risk factors, but was
diagnosed with colorectal cancer (cT3 N1 M0) and
underwent recent neoadjuvant chemotherapy with
5‑FU (9500 mg by continuous infusion over a period
of 120 h) until 1 day before his acute presentation.
His physical examination revealed hypotensive blood
pressures (89/58 mmHg) and heart rate at rest of
95 bpm. There was distension of the jugular veins
with normal heart sounds. The electrocardiogram
documented sinus rhythm at 95 bpm with non‑significant
ST‑elevation in leads II, III, aVF. High‑sensitive troponin T
(60 ng/L; upper reference value 14 ng/L) and creatine
kinase‑MB fraction (0.74 µmol/L*s; upper reference
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DOI:
10.4103/1995-705X.132144
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Höllriegel, et al.: 5-fluorouracil-induced acute heart failure
hemodynamic stabilization was evident and medical
heart failure treatment including angiotensin‑converting
enzyme‑inhibitor, diuretics and spironolactone was
commenced. After 4 days with ECMO therapy,
left‑ventricular ejection fraction improved to 45% and
lactate levels were in normal ranges (<2 mmol/L).
Therefore, ECMO‑flow was reduced slowly up to
1.5 L/min. Due to the stable lactate levels (<2 mmol/L)
successful ECMO explantation was performed on day 5.
The following course was uncomplicated with
normalization of blood pressures and no signs of
heart failure. Eight days after admission, he was
transferred to the normal ward. Left‑ventricular ejection
fraction was now recovered to a normal value of
60% [Figure 2a and b]. For confirmation and further
differential diagnosis cardiac, magnetic resonance
imaging (MRI) was performed. The MRI showed a
normal sized left ventricle (left ventricular end‑diastolic
volume: 149 mL; normal value 102‑235 mL) with normal
ejection fraction of 57% and without any specific wall
value 0.41 µmol/L*s) were slightly elevated. Creatinine
kinase showed a normal value of 0.93 µmol/L*s (upper
reference value 3.17 µmol/L*s).
Initial transthoracic echocardiography (TTE) showed
a normal sized left ventricle (left‑ventricular end‑diastolic
diameter: 48 mm, left‑ventricular end‑diastolic volume:
103 mL) with global hypokinesia and severely decreased
left‑ventricular systolic function [left‑ventricular ejection
fraction: 16%; [Figure 1a and b]. Pericardial effusion
and relevant valve disease were excluded. Coronary
arteries were normal at angiography.
One day after admission, patient had persistent
hypotension with increasing lactate levels as a sign of
peripheral malperfusion. On repeat echocardiographic
examination, left‑ventricular systolic function was found
to have further decreased with a left‑ventricular ejection
fraction of <10%. Due to the progressive cardiogenic
shock, we decided to treat this condition by the use of an
extracorporeal membrane oxygenation (ECMO) support
by percutaneous implantation. On ECMO support,
a
b
Figure 1: Transthoracic echocardiography on day 1 (a) Apical four‑chamber view during diastole, (b) Apical four‑chamber view during
systole (There is global hypokinesia with severely impaired thickening of the left ventricular wall in systole)
a
b
Figure 2: Transthoracic echocardiography on day 10 (a) Apical four‑chamber view during diastole, (b) Apical four‑chamber view during
systole. There is a normal thickening of the left ventricular wall in systole
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Höllriegel, et al.: 5-fluorouracil-induced acute heart failure
motion abnormality. T2‑weighted imaging revealed mild
degree of generalized myocardial edema. Furthermore,
T1‑weighted imaging showed pronounced early contrast
enhancement, indicating some degree of myocardial
hyperemia. No signs of myocardial scar or necrosis
were detectable. Patient was discharged from hospital
in a stable cardiac condition without symptoms of heart
failure 11 days after admission.
counterpulsation was shown not to reduce 30‑day
mortality in patients with cardiogenic shock complicating
myocardial infarction.[9] In our case with progressive
cardiogenic shock, the most effective pre‑ and afterload
reduction was necessary. Therefore, we decided to use
ECMO ‑ the most potent form of acute cardiorespiratory
support, which enables complete relief of cardiac workload
and prevents high‑dose usage of sympathomimetics.
DISCUSSION
CONCLUSION
This report describes a patient with no history of
cardiovascular disease who experienced acute
left‑ventricular failure after administration of 5‑FU.
Cardiac complications ranging from angina pectoris to
cardiogenic shock after chemotherapy with 5‑FU are not
rare.[1‑3] Coronary vasospasm, endothelial damage with
consequent thrombus formation, increased myocardial
oxygen demand, block of myocardial cell metabolism and
Tako‑Tsubo‑like syndrome with supraphysiologic levels
of plasma catecholamines are discussed as potential
pathogenetic mechanisms.[1,4] Our patient did not report
any angina and obstructive coronary lesions were
excluded by angiography. Echocardiography did not
reveal an apical ballooning as common in Tako‑Tsubo‑like
syndrome. The cardiac MRI of our patient strengthens
the concept of an additional temporary myocardial
inflammation. Increased global myocardial edema
and evidence of myocardial hyperemia are compatible
with a regressive inflammation.[5] Unfortunately, the
MRI could not be performed in the acute setting with
severely decreased left‑ventricular function due to
ECMO‑therapy and therefore, the extent of myocardial
edema and hyperemia might be underestimated.
Treatment of cardiogenic shock is still a therapeutic
challenge, especially if coronary artery disease was
excluded. Usually, sympathomimetics are used as first
line therapeutics, but several disadvantages in their
use have to be taken into account. Sympathomimetics
induced vasoconstriction can lead to perfusion mismatch
or even deficit within the microcirculation and metabolic
acidosis due to an increased oxygen demand can be
observed regularly.[6] In addition, some studies give
evidence that use of sympathomimetics is directly linked
to enhanced systemic inflammatory response due to an
increased interleukin‑6 expression.[7,8]
In our case with unclear pathogenesis of cardiogenic
shock, we decided to use a mechanical hemodynamic
support (intraaortic balloon counterpulsation or ECMO)
to avoid above mentioned disadvantages with the use
of sympathomimetics, especially with the knowledge
about inflammation as a possible cause of 5‑FU induced
left‑ventricular dysfunction. Recently, intraaortic balloon
Cardiogenic shock should be taken into consideration
as a possible complication secondary to chemotherapy
with 5‑FU, even in patients without a history of
cardiovascular disease. To the best of our knowledge,
this is the first report of an ECMO support in this kind of
chemotherapeutic induced cardiogenic shock. ECMO
support enabled complete relief of cardiac workload and
together with medical therapy for heart failure, complete
recovery of cardiac function was possible.
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Source of Support: Nil, Conflict of Interest: None declared.
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