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Duloxetine-Induced Takotsubo Cardiomyopathy

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Title: Duloxetine-Induced Takotsubo Cardiomyopathy


1
Duloxetine-Induced Takotsubo Cardiomyopathy
  • Richard Perry, Pharm.D.
  • Assistant Professor Of Pharmacy Practice
  • Arnold Marie Schwartz College of Pharmacy and
    Health Sciences
  • Long Island University
  • Brooklyn, New York

2
Takotsubo Cardiomyopathy Overview
  • Type of stress-induced cardiomyopathy
  • Also known as transient left ventricular apical
    ballooning, cardiac syndrome X and broken heart
    syndrome
  • Japanese name meaning octopus trap
  • Under recognized disease state
  • May mimic an acute myocardial infarction (AMI)
  • Found in 1-2 of patients with suspected AMI

3
Clinical Presentation
  • Most commonly seen in postmenopausal women
  • Chest pain
  • Dyspnea
  • ECG changes
  • ST-segment elevation
  • QT Prolongation
  • ECHO findings
  • Left ventricle ballooning of apical and
    midventricular segments, hyperkinetic basal
    segment
  • EF Severely decreased
  • Laboratory Findings
  • CKMB, troponin, catecholamine levels
  • Normal coronary arteries or absence of acute
    plaque rupture

4
Cardiac Wall Abnormalities
Scott et al. Circulation. 2005 Feb
1111(4)472-9.
5
Pathophysiologic Triggers
  • Specific cause is unknown
  • Possibly catecholamine mediated
  • Epicardial vessel spasm
  • Reduction in myocardial oxygen supply
  • Commonly preceded by acute emotional or physical
    stress
  • Vigorous excitation
  • Acute medical illness
  • Acute cocaine intoxication

6
Duloxetine (Cymbalta)
  • Serotonin and norepinephrine reuptake inhibitor
    (SNRI)
  • FDA approved for
  • Major depressive disorder
  • Diabetic peripheral neuropathic pain (DPNP)
  • Generalized anxiety disorder
  • Initial dose for DPNP 60 mg/daily
  • Metabolized through CYP450 1A2 and 2D6

7
Case Report
  • 60 y/o HF (Ht, 160 cm Wt, 58.6 kg) admitted to
    emergency department
  • CC Chest pain, lightheadedness, nausea and
    diaphoresis
  • PMH Type 2 diabetes mellitus, DPNP,
    hypertension, hypothyroidism, s/p UTI, multiple
    hernia and uterine fibroid surgeries
  • Medications on admission Duloxetine 60 mg QAM,
    levothyroxine, insulin, lisinopril, aspirin,
    metformin, repaglinide

8
Case Report cont
  • All Iodine (Rash)
  • FH Unknown
  • SH H/O alcohol use, unemployed, living alone
  • PTA Completing course of ciprofloxacin (CYP450
    1A2 inhibitor) for UTI

9
Time Course of Reaction
Outpatient Hospital Day Event
1 AM Initiated duloxetine 60mg QAM for DPNP PM Felt lightheaded and nauseous
2 AM Worsening symptoms accompanied by dizziness upon standing
3 AM Pt fell during an episode of dizziness 5 hrs later symptoms worsened and pt went to hospital
10
Presentation at Hospital
  • Developed left sided chest pain
  • Nonradiating, 7/10 intensity, pushing quality
  • Diaphoretic, experiencing palpitations
  • Denied SOB
  • Vital Signs
  • BP, 155/105 mmHg HR, 114 bpm RR, 16 bpm Temp,
    98.4oF
  • Lungs CTA B/L

11
Presentation at Hospital cont
  • ECG anterior and inferolateral ST elevations, T
    wave inversions and prolonged QTc interval (536
    msec)
  • Pertinent lab values on admission
  • Troponin I, 3.343 ng/mL ref. range lt/0.059
    ng/mL
  • Norepinephrine, 3492 pg/mL ref. range 70-750
    pg/mL
  • C-Reactive Protein, 6.4 mg/L ref. range 0.215-3
    mg/L
  • Creatine kinase, 72 U/L ref. range 35-155
    U/L

12
Presentation at Hospital cont
  • Believed to have AMI
  • Given aspirin, nitroglycerin, heparin, metoprolol
    and clopidogrel
  • Rapid symptomatic improvement seen
  • Pt admitted to hospital
  • Duloxetine continued
  • Scheduled for cardiac catheterization and ECHO

13
Cardiac Study Findings
  • Cardiac Catheterization
  • Normal coronary arteries
  • ECHO
  • Akinesis of LV apex
  • Hyperdynamic motion of LV basal segments
  • EF of 30
  • Diagnosis of Takotsubo cardiomyopathy made
  • Heparin continued due to stasis of left
    ventricle, to prevent thrombus formation

14
Hospital Time Course
Inpatient Hospital Day Event
1-6 Resolution of presenting symptoms, episodes of orthostatic hypotension, BP meds d/c, resulting hypertension
7 Duloxetine d/c, APAP or APAP-codeine for DPNP, BP meds restarted
8 EF to 35
9 Resolution of orthostatic hypotension
10 Discharged, warfarin prescribed to prevent thrombus formation in LV, pregabalin prescribed for DPNP
15
Patient Case Follow-Up
  • 39 days post-discharge
  • EF 70
  • LV wall segments contract normally
  • Slight impaired relaxation of LV
  • Warfarin therapy continued

16
Discussion
  • Severe cardiovascular side effects uncommon with
    duloxetine
  • Possible inhibition of duloxetine metabolism by
    ciprofloxacin
  • Reaction likely due to norepinephrine surge
  • Temporal and causal association found between
    duloxetine initiation and onset of Takotsubo
    cardiomyopathy
  • Naranjos nomogram score 6 probable case of
    duloxetine-induced Takotsubo cardiomyopathy

17
Conclusions
  • Takotsubo cardiomyopathy is generally transient
    and reversible but may mimic AMI
  • Clinicians must be cognizant that duloxetine may
    cause Takotsubo cardiomyopathy
  • Avoid concurrent use of CYP 450 1A2 and 2D6
    inhibitors with duloxetine

18
  • Thank You
  • Questions?

McCollough. Crit Care Nurse. 2007 Dec27(6)20-7
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