Duloxetine-Induced Takotsubo Cardiomyopathy

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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

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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

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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

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Cardiac Wall Abnormalities
Scott et al. Circulation. 2005 Feb
1111(4)472-9.
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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

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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

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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

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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

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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
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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

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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

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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

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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

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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
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Patient Case Follow-Up

• 39 days post-discharge
• EF 70
• LV wall segments contract normally
• Slight impaired relaxation of LV
• Warfarin therapy continued

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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

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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

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• Thank You

• Questions?

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