2.6 Imaging examinations
CT showed bilateral lung exudation and pleural effusion (Figure 4).
Spiral CT pulmonary angiography showed no abnormality.
Echocardiography showed mild
tricuspid regurgitation with elevated pulmonary artery systolic
pressure(33mmHg). No clinically significant abnormality was found by
emergency electrocardiography (ECG).
FINAL DIAGNOSIS
Based on the clinical signs and elevated BNP, the patient was diagnosed
with acute heart failure clinically7, while pulmonary
embolism was excluded based on the results of spiral CT pulmonary
angiography.
TREATMENT
The patient was transferred from the ward to the intensive care unit and
noninvasive positive-pressure ventilation, diuresis, and anti-infective
therapy were administered immediately.
OUTCOME AND FOLLOW-UP
On the morning of postoperative day 3, all the symptoms were
significantly relieved, with the oxygen saturation increasing to 100%.
Plasma BNP, hs-cTnT and D-dimer levels also returned to normal.
Echocardiography also showed no abnormality at this time.
DISCUSSION
MAS is a rare noninherited genetic disease characterized by polyostotic
fibrous dysplasia, café-au-lait spots, and sexual precocity, which was
first described by McCune and Bruch and by Albright8.
In recent years, endocrine abnormalities including hyperthyroidism,
growth hormone excess, and Cushing syndrome, as well as nonendocrine
abnormalities such as cardiac and hepatic diseases have also been
reported1, 9. Based on the genetic analysis of MAS
patients, the mutation of guanine nucleotide-binding protein
α-stimulating activity polypeptide (GNAS) is widely accepted as the
major pathological mechanism of MAS10. The most common
mutation site of GNAS is the amino acid Arg 201, which is replaced by
Cys or His or Ser or Gly6, 10, 11. It is reported that
the mutation of GNAS affects somatic cells but not genital cells, while
the number of somatic cells mutated in specific tissues and organs
varies11-14. Thus, MAS patients could present with
variable clinical manifestations, which depend on the location, cell
type and numbers of the mutated cells4, 9, 15.
Polyostotic fibrous dysplasia is the main skeletal manifestation of MAS,
ranging from 46% to 98% according to different
reports4, 16. The femur and craniofacial region are
the most commonly affected. Most of the patients with MAS have at least
one fracture, and even multiple fractures, especially between 6 and 12
years old4. In addition to bone
fractures, fibrous dysplasia in
the appendicular skeleton can lead to pain, limping, and deformities of
the weight-bearing bone, while fibrous dysplasia in the craniofacial
bones can lead to painless lumps or facial asymmetry. Besides,
compressive syndrome and scoliosis caused by fibrous dysplasia have also
been reported2. As the progression of fibrous
dysplasia may bring about deformities as well as physical impairment
such as limping and the need for a wheelchair, orthopedic surgical
intervention is usually required for the recovery of motor
functions2, 3.
Cardiovascular involvement, as a rare event in MAS patients, is one of
the fatal conditions that can present as tachycardia, hypertension,
cardiac hypertrophy, and even sudden death4, 9. Only
one study has reported heart failure as the manifestation of cardiac
involvement17. Previously, cardiac abnormalities in
patients with MAS were mostly interpreted as a complication of endocrine
disturbances9, 17. Subsequently, hypertrophied
myocytes with Gs mutation in the macroscopically normal heart of MAS
patients diagnosed with sudden death at autopsy illustrated that the
mutation of heart tissue is a more convincing explanation for cardiac
manifestations in MAS, rather than the complication of endocrine
abnormalities4, 9. However, the underlying mechanism
of cardiovascular involvement in MAS is not entirely clear. It is
reported that mutation of GNAS can cause overproduction of cyclic AMP
and enhanced phosphorylation of calcium channels, which subsequently
increases the Ca2+ permeability of myocardial cells.
As a result of intracellular Ca2+ accumulation,
cardiac myocytes are continuously overactivated and cause increased
heart rate and myocardial contractility, which eventually induce cardiac
dysfunction[4,20].
According to the acute heart failure assessment reported by the
literature, our patient could be diagnosed with acute heart failure
based on elevated NT-proBNP, interstitial edema, dyspnea and absence of
fever18. For differential diagnosis, pulmonary
embolism has been excluded through Spiral CT pulmonary angiography.
Normal ECG and no chest pain also do not agree with acute coronary
syndrome or arrhythmia due to reduced hemoglobin postoperatively.
Pulmonary complications were not consistent with extremely high BNP.
Considering Swan-Ganz catheter or nuclear imaging is only recommended
for non-classical acute heart failure like without BNP elevated or the
treatment is not effective19, we did not perform them
on our patient.
To the best of our knowledge, postoperative acute heart failure in a
young patient without a history of cardiac disease and cardiac
morphology abnormality has not yet been reported. In consideration of
the fact that macroscopic findings of the Gs mutated heart are often
inconspicuous in the clinic4, as well as the
impossibility of acute heart failure for a patient without a history of
cardiovascular abnormalities at such a young age, latent cardiovascular
involvement of MAS seems to be a reasonable interpretation for the acute
heart failure of the present patient.
We proposed two potential mechanisms for acute heart failure in this
young patient with limited fluid replacement volume based on the known
cardiotoxicity of cAMP and Ca2+20. Firstly, long-term
cAMP overload may induce myofilament calcium desensitization of the
cardiac myocytes through increased protein kinase A. Therefore, the
desensitized cardiac myocytes cannot respond effectively to the
increased calcium influx to enhance the cardiac contractibility when the
fluid load increases21, 22. Secondly, long-term
Ca2+ overload may have a negative impact on the
compliance of the heart due to the hypertrophied myocytes and increased
myocardial contractility23. However, we admit that
further investigation is required to explore further the exact
mechanism.
The present report was limited because we could not perform genetic
analysis of cardiomyocytes due to regulatory and ethical concerns.
CONCLUSIONS
Many patients with MAS are admitted to orthopedic departments for
surgical intervention. Therefore, it is important for orthopedic
surgeons to be aware of polyostotic fibrous dysplasia and other rare but
fatal manifestations, such as cardiac involvement. To the best of our
knowledge, our report represents the first case of a young woman with
MAS and acute heart failure after proximal femur osteotomy, with no
cardiovascular abnormality or history of cardiovascular disease. As
latent cardiovascular involvement of MAS was considered to be the major
cause of this case, we recommend more detailed preoperative
cardiovascular screening for MAS patients. We believe that this case
report and the literature review will help orthopedic surgeons make a
more reasonable prognostic assessment, and subsequently reduce the risk
of medical dispute by further understanding this rare but fatal event of
MAS.