Discussion:
The etiology of pericardial effusion and cardiac tamponade is often
idiopathic. Cubero et al states the three major causes of large
pericardial effusions were idiopathic pericarditis, tuberculous, and
neoplastic origin in descending order of incidence. Similar results were
found in Sagristà-Sauleda et al, attributing the most common cause of
large pericardial effusions to idiopathic pericarditis, followed by
iatrogenic, and malignant with the latter having the highest likelihood
of becoming cardiac tamponade [9,10]. Among the majority of data
pertaining to etiology, drug-induced pericardial effusion seems to be
either excluded or dismissed under the umbrella of idiopathic.
Management of pericardial effusion and cardiac tamponade is
case-dependent and essentially remains the same with either
pericardiocentesis, pericardial window or pericardiectomy. However, rare
etiologies in certain clinical scenarios may warrant a different
approach to management. The progression of a pericardial effusion into a
cardiac tamponade could impose catastrophic clinical outcomes,
especially in patients with co-morbid conditions such as malignancy that
may hinder any invasive intervention and augment the hemodynamic
instability of cardiac tamponade [11,12]. Markiewicz et al found
that predictors of long-term survival relied on the prognosis of the
primary illness, regardless of the treatment modality. This poses a
challenge since the majority of pericardial effusion and cardiac
tamponade cases are attributed to an idiopathic etiology, as previously
mentioned.
The diagnosis of cardiac tamponade continues to rely on
echocardiography, which apart from identifying the specific signs, also
aims to evaluate the size, distribution, presence of intrapericardial
adhesions or clot, the feasibility of pericardiocentesis, and the
evolution of the pericardial effusion. Sanjay et al concluded that the
sensitivity, specificity and positive predictive value of RV diastolic
collapse is 93%, 100% and 100%, respectively. On the other hand,
Rifkin et al states that although sensitivity of RV diastolic collapse
increased in relation to the severity of cardiac tamponade, its
specificity remained higher and constant at 88% whether the tamponade
was early, moderate or severe. RV collapse takes place in early
diastole, and as the cardiac tamponade progresses, it could span the
entirety of diastole [15-17]. Although our patient’s
echocardiography showed tamponade physiology, the classic beck’s triad
of muffled heart sounds, presence of JVD, and hypotension did not
completely manifest and the patient’s only recurrent complaint was
shortness of breath requiring minimal oxygen supplementation by nasal
cannula. However, decompensation risk remained very high. In practice,
the clinical symptoms and signs of cardiac tamponade are a good compass
of suspicion, but they are not reliable without echocardiographic
confirmation, especially since they could be present in other
overlapping conditions such as acute or chronic obstructive airway
disease, pulmonary embolism, tension pneumothorax, large pleural
effusions, effusive constrictive pericarditis, RV infarction,
restrictive cardiomyopathy, extreme obesity, or tense ascites. In
addition, the combination of classic and non-classic cardiac tamponade
signs and symptoms are most likely to be absent in gradually developing
cardiac tamponade [18]. Thus, given our patient’s sustained and
relative hemodynamic stability, her pericardial effusion most likely
developed in a gradual manner over days to weeks following the change in
her ET regimen by the introduction of anagrelide, allowing the
pericardium to stretch and accommodate the large effusion. The only
identifiable event was the discontinuation of hydroxyurea and the
initiation of anagrelide three weeks prior to presentation, which is
consistent with enough lead-time for a gradual, large pericardial
effusion to develop and be reflected with the patient’s progressive
feeling of being unwell since the change. It is important to note that
the patient had previously been placed on an anagrelide trial with an
intolerant outcome described by the patient as pleuritic chest pain,
shortness of breath and palpitations. The recent switch to anagrelide
was a re-trial by the patient’s primary hematology team in an attempt to
reevaluate tolerability in order to reduce her sustained,
hydroxyurea-refractory thrombocytosis at the time.
Pericardial effusion was reported as a rare adverse reaction of
anagrelide during its trials. Its incidence among its current users is
unknown and the mechanism behind it is unclear [13]. In conditions
indicated to receive anagrelide such as our patient’s ET, management of
drug-induced cardiovascular events becomes a challenge in the setting of
withdrawing the insulting medication. ET is known to put patients at
risk for both thromboembolic as well as bleeding events. The
thromboembolic events stem from abnormalities in platelet morphology,
including its membrane, as well as derangements in arachidonic acid
metabolism, and the bleeding nature of the disease is a result of
qualitative platelet dysfunction as well as acquired Von Willebrand
disease secondary to diminished large Von Willebrand multimers [8,
13].
Thus, at baseline, ET patients are at a higher risk for cardiovascular
thromboembolic events in addition to a low threshold of bleeding,
potentially complicating the course of, in our case, pericardial
effusion and demonstrating an obstacle in the face of required invasive
procedures. In chronic, stable pericardial effusions of large volume as
well as cardiac tamponade, a complete benefit versus harm stratification
that addresses both the myeloproliferative disorder and the
cardiovascular pathology must be considered before initiating a medical
decision concerning either one. Our case represents a complex scenario
with multidisciplinary collaboration that could become more frequent as
anti-platelet aggregation therapies become the dominantly preferred
approach to hematologic disorders in patients at risk of cardiovascular
disease and its escalation.