Characterization of Sympathetic Nerve Activity in Stress Cardiomyopathy

Stress (Takotsubo) cardiomyopathy (SC) is a peculiar form of acute, reversible myocardial dysfunction predominantly affecting the apical and mid left ventricular segments. This was originally described in Japan but is increasingly recognized all over the world especially in older women. There is evidence to support that excess sympathetic activation and catecholamine surges are potential mechanisms that cause this temporary myocardial 'stunning'. The amount of catecholamines in circulation of patients with SC was 2 to 3-fold higher when compared to subjects with acute myocardial infarction related equivalent cardiac dysfunction [Wittstein, et al. NEJM, 2005].

In our institution over the last two to three years we have identified more than a dozen patients with stress cardiomyopathy. This diagnosis has been confirmed by echocardiographic documentation of normalization of left ventricular function over a course of few days to weeks. Our overarching goal is to further characterize these individuals with the hope of identifying risk factors and developing strategies to prevent the occurrence of SC in situations where the likelihood in susceptible individuals may be high.

• Device: Sympathetic Nerve Activity
  Resting Sympathetic Nerve Activity
• Behavioral: Mental Stress Test (Color Word Test)
  A printed word will be shown to the subject, displayed in a color different from the color it actually names. The subject will be asked to say the color that the word is printed in as quickly as possible. For example if the word "green" is written in blue ink, they will say "blue." This mental stress procedure will be used to cause brief changes in heart rate and blood pressure.
• Drug: The Modified Oxford Technique for Baroreflex Sensitivity
  Sodium nitroprusside (100 µg) will be infused intravenously as a bolus, followed 60 seconds later by a bolus of phenylephrine hydrochloride (150 µg). Infusion of nitroprusside will decrease blood pressure approximately 10-15 mmHg below baseline values. Subsequent phenylephrine infusion will increase blood pressure approximately 10-15 mmHg above baseline values. Nitroprusside and phenylephrine have been used extensively to assess baroreflex sensitivity in healthy as well as heart failure populations. Additionally, the dosages being used have been shown to minimize the risk of excessive decreases or increases in blood pressure.
• Other: Cold Pressor Test
  The subject will be asked to place their hand in ice water for 2 minutes. This procedure will be used to cause transient changes in sympathetic nerve activity, heart rate and blood pressure.
• Device: Echocardiographic evaluation
  Transthoracic echocardiography with 2D, color and pulse Doppler will be employed in all of our subjects. Baseline left ventricular function, systolic as well as diastolic, will be quantified.

• Experimental: Study group
  Subjects with documented stress cardiomyopathy who would serve as the study group.
  Interventions:

  • Device: Sympathetic Nerve Activity
  • Behavioral: Mental Stress Test (Color Word Test)
  • Drug: The Modified Oxford Technique for Baroreflex Sensitivity
  • Other: Cold Pressor Test
  • Device: Echocardiographic evaluation
• Active Comparator: Control
  Control subjects will be age and sex matched otherwise healthy people with no prior cardiac disease or other severe medical conditions.
  Interventions:

  • Device: Sympathetic Nerve Activity
  • Behavioral: Mental Stress Test (Color Word Test)
  • Drug: The Modified Oxford Technique for Baroreflex Sensitivity
  • Other: Cold Pressor Test
  • Device: Echocardiographic evaluation

Inclusion Criteria:

• Diagnosis of stress cardiomyopathy in the past

Exclusion Criteria:

• CAD, PCI or CABG
• Cardiac dysfunction
• Heart failure
• Significant arrhythmias
• Severe COPD
• Diabetic neuropathy
• Pregnancy