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Gowdar et al. Diabetes mellitus and takotsubo cardiomyopathy

stunning, diffuse multi-vessel coronary spasm, current discussion.
microvascular dysfunction and estrogen deficiency. [4]
Retrospective studies
An increased catecholamine surge leading to A large international collaborative systematic review
exaggerated cardiac sympathetic stimulation has sought to evaluate the prevalence of comorbidities,
long been thought to be a plausible mechanism of TC cardiovascular and others, in TC patients. The authors
[8]
pathogenesis. Animal studies using rat models have evaluated 19 large case series between 2007 and 2013
provided further evidence that left ventricular apical or which included 1,109 patients with TC. Among the
midventricular dysfunction in TC patients could be a 1,109 patients with TC (86% females), hypertension
result of catecholamine mediated effects on cardiac was present in 54% (range 27-83%), dyslipidemia in
beta receptors, particularly the pleiotropic β2 receptors. 32% (range 7-59%), but DM in only 17% (prevalence
This is related to epinephrine and isoprenaline ranging between 4-34%). Of all the 19 studies, 11
mediated switching of beta receptor activation from demonstrated DM prevalence to be < 14%, with 6
cardiostimulation to cardioinhibitory pathways, via studies demonstrating a prevalence rate of DM < 10%.
the activation of Gi proteins, instead of Gs proteins. Although there was no control group for comparison
[5]
Exaggerated sympathetic stimulation has been of the TC patients to the general population, or to the
inferred from markedly elevated plasma catecholamine population of acute myocardial infarction (MI) patients,
levels, both epinephrine and norepinephrine, in TC the authors concluded that traditional cardiovascular
patients. The specific mechanism of catecholamine risk factors are commonly prevalent in TC patients, with
[5]
mediated myocardial stunning is unclear, with possible frequencies similar to those seen in acute MI patients.
[8]
mechanisms being decreased myocardial blood flow However, the prevalence of DM in this study appeared
or direct catecholamine myocardial toxicity. Coronary to correlate with the rates demonstrated by a large
microvascular dysfunction leading to impaired metanalysis, which led to support the hypothesis of
[5]
microcirculatory perfusion and myocardial stunning DM being a protective factor in TC patients.
has also been thought to play a significant role in the
development of TC. [4,6,7] Human and animal studies
have illustrated the primary role of autonomic nerves A Spanish study comprising 328 TC patients compared
innervating the heart and a secondary role of the the “primary” (265 patients) and “secondary” (63
[9]
adrenal medulla with sympathetic and parasympathetic patients) forms of TC. Primary TC was described as
influences on neurovisceral myocardial injury. Neural that triggered by a psychic stress or without stressful
[5]
disconnection between the brain and the heart in brain stimulus. Additionally, secondary TC was described
death and cardiac transplantation have been shown as the one triggered by the presence of physical
to blunt neuromyocardial damage and cause an stressors such as sepsis, intracranial hemorrhage
amelioration of electrocardiographic abnormalities. or cerebrovascular accident, severe trauma,
[5]
Similarly, diabetes mellitus (DM) is associated bronchospasm, surgery or other critical illnesses.
with autonomic neuropathy and thus may exert an Patients with secondary TC forms demonstrated more
independent potential influence on the pathogenesis hospital complications, higher major adverse cardiac
of TC. This article aims to review the association events, higher mortality and higher rates of recurrence.
[1]
between DM and TC, based on the knowledge gained The prevalence of hypertension was 68.3% in the
from the recent studies. primary TC cohort and 60.3% in the secondary TC
cohort. Dyslipidemia was seen in 44.9% and 41.2% in
DATA the primary and secondary forms of TC respectively.
The prevalence of DM was overall low (13.1%), and
We searched PubMed/Medline, Scopus and Google the prevalence in the primary and secondary forms of
Scholar for original articles published between TC, was 12.8% and 14.2%, respectively. Hypertension
[1]
1990 and 2016, focusing on TC and DM. The was slightly more and DM was slightly less prevalent
keywords used to conduct the relevant literature in the “primary” TC group compared to the “secondary”
search, alone and/or in combination, were “takotsubo TC group. [9,10] Thus, this study further underscores the
cardiomyopathy”, “stress cardiomyopathy”, “apical low rates of DM in TC patients.
ballooning syndrome”, “diabetes”, “diabetes mellitus”,
“prevalence”, “incidence” and “association”. All In another small retrospective study, the role of
articles published in the English language were coronary microvascular function in patients with TC was
then independently reviewed. Papers included were compared with controls without CAD, using invasive
original research, review, case reports and relevant angiography and TIMI frame counts. [11] The prevalence
correspondences. After a comprehensive review of of DM was low (only 6.25%), again suggesting that the
the articles selected, we used literature relevant to our presence of DM may confer a protective effect in the
130 Vessel Plus ¦ Volume 1 ¦ September 26, 2017