BROKEN HEART SYNDROME
TA KOT S U B O C A R D IOMYOPATH Y
A P IC A L BA L LOON IN G S Y N D ROM E
S T R E S S C A R D IOM YOPAT HY
Maryann Hurles
SYMPTOMS OF BROKEN
HEART SYNDROME
•Dyspnea
• Difficult or painful breathing
•Chest pain
•Syncope
• temporary loss of consciousness caused by a
fall in blood pressure
•ST segment elevation
• myocardial ischemia or infarction.
•Prolonged QT interval
• fast, chaotic heartbeats
•Elevated troponin
• myocardial injury
WHAT TRIGGERS A BROKEN HEART?
Your boyfriend breaking up with you…Just kidding…maybe?
Job loss
Domestic abuse
Unexpected death of a love one
Frightening medical diagnosis
Losing/winning a lot of money
Surprise party
Physical stressors
Asthma attack
Car accident
Major surgery
Treatments
• Angiotensinconverting enzyme
(ACE) inhibitor
• Beta blockers
• Diuretics.
Surge of stress hormones
Epinephrine
Sympathetic NS activation
Duloxetine and Venlafaxine
 selective serotonin and
norepinephrine reuptake inhibitor
antidepressant.
DRUGS THAT CAN CONTRIBUTE
TO BROKEN HEART SYNDROME
Levothyroxine
slows heart rate
makes the arteries less elastic
blood pressure rises
Multiple cased of BHS in the
same family
Recurrent cases indicate
genetics
Association between BHS
and SNPs in genes
associated with sympathetic
stress.
GENETIC COMPONENT
(STILL QUESTIONABLE)
Exchange of amino acids in
the β1-adrenergic receptor
and G-protein-coupled
receptor kinase 5
 Regulate cardiac sympathetic
stimulation
WHAT IS LOOKS LIKE
Octopus in a Jar
IN THE NEWS
“WAS IT A BROKEN HEART THAT LANDED GEORGE H.W. BUSH, THE 41ST PRESIDENT,
IN THE HOSPITAL JUST A DAY AFTER THE FUNERAL OF HIS WIFE, BARBARA?”
The Bushes were married for 73 years
Speculation swirled that Mrs. Bush’s
death must have sent him into a
downward medical spiral.
Mr. Bush reportedly had an infection
that flared dangerously, and he is quite
frail.
Any number of factors could have
contributed to his hospitalization.
Can a broken heart really cause a
disease?
THE STUDIES
Minnesota Living with Heart Failure
Questionnaire
Patients who suffered an acute
takotsubo episode at least a year ago.
Impaired cardiac energetic status
Reduced maximal oxygen consumption
on exercise because of significant
cardiac limitation
Significant impact on quality of life
Figure 3. Corrected phosphocreatine (PCr)/[gamma]adenosine triphosphate ([gamma]ATP) ratio in patients
with takotsubo cardiomyopathy and matched control
subjects. A, All subjects. B, Excluding subjects with
hypertension. C, Excluding subjects with diabetes
mellitus. D, Excluding subjects with both hypertension and
diabetes mellitus. Data shown as median, 25th, and 75th
percentiles and maximum and minimum (whiskers).
Representative spectral analyses. E, Patient with previous
takotsubo cardiomyopathy. F, A healthy control. The
takotsubo patient shows a reduction in PCr/[gamma]ATP
ratio.
CATECHOLAMINE-DEPENDENT ΒETA-ADRENERGIC
SIGNALING
oFluorescence resonance energy transfer
(FRET) is a phenomenon in which energy is
transferred from an excited fluorophore, the
donor, to a light-absorbing molecule, the
acceptor.
oSomatic cells of patients with TTS and
control subjects were reprogrammed to iPSCs
and differentiated into CMs
(A and B) Representative cAMP-FRET traces from the Epac1-cAMP-FRET sensor in adenovirally
transduced iPSC-CMs from patients with TTS and control subjects stimulated with increasing b-AR
agonist concentrations (100 to 1 mmol/l Iso). The subsequent maximal FRET response was induced by
the unselective phosphodi- esterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX) (100 mmol/l).
oThree-month-old CMs were subjected to
catecholamine stimulation to simulate
neurohumoral overstimulation
oWe investigated beta-adrenergic signaling
and TTS cardiomyocyte function.
Symptoms can often seem like
a myocardial infarction.
Can be triggered by any
surprising life altering event.
Certain prescriptions can cause
BHS.
Could potentially be genetic,
but lot’s of conflicting evidence.
Can impact quality of life.
Beta-adrenergic reception
plays a large role.
THAT’S A WRAP
Scientists are still at odds about
the Broken heart aspect of this
disease!
REFERENCES
Broken heart syndrome. (2016, November 05). Retrieved from https://www.mayoclinic.org/diseases-conditions/broken-heartsyndrome/symptoms-causes/syc-20354617
Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, et al. Natural history and expansive clinical profile of stress
(tako-tsubo) cardiomyopathy. J Am Coll Cardiol. 2010;55(4):333–41.
Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of Takotsubo (stress)
cardiomyopathy. N Engl J Med. 2015;373(10):929–38.
Vriz O, Minisini R, Citro R, Guerra V, Zito C, De Luca G, et al. Analysis of beta1 and beta2-adrenergic receptors polymorphism in
patients with apical ballooning cardiomyopathy. Acta Cardiol. 2011;66(6):787–90.
Spinelli L, Trimarco V, Di Marino S, Marino M, Iaccarino G, Trimarco B. L41Q polymorphism of the G protein coupled receptor kinase 5
is associated with left ventricular apical ballooning syndrome. Eur J Heart Fail. 2010;12(1):13–6.
Kolata, G., & Carey, B. (2018, April 24). With George H.W. Bush Hospitalized, the World Wonders: Is It a Broken Heart? Retrieved
from https://www.nytimes.com/2018/04/24/health/george-barbara-bush-grief-health.html
Scally, Caroline (03/2018). "Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo)
Cardiomyopathy.". Circulation (New York, N.Y.)(0009-7322), 137 (10), p. 1039.
Borchert, Thomas (08/2017). "Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo
Cardiomyopathy.". Journal of the American College of Cardiology (0735-1097), 70 (8), p. 975.