Characterization of Sympathetic Nerve Activity in Stress Cardiomyopathy

Study Overview
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Brief Summary
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Stress (Takotsubo) cardiomyopathy (SC) is a peculiar form of acute, reversible myocardial dysfunction predominantly affecting the apical and mid left ventricular segments. In this institution over the last two to three years the investigators have identified more than a dozen patients with stress cardiomyopathy. The investigators' overarching goal is to 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.

Detailed Description
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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 this institution over the last two to three years the investigators 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. The investigators' 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.

Official Title
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Characterization of Sympathetic Nerve Activity in Stress Cardiomyopathy

Conditions
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Cardiomyopathy

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of stress cardiomyopathy in the past Exclusion Criteria: Coronary artery disease (CAD), primary coronary intervention (PCI) or coronary artery bypass graft (CABG) Cardiac dysfunction Heart failure Significant arrhythmias Severe chronic obstructive pulmonary disease (COPD) Diabetic neuropathy Pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Subjects with documented stress cardiomyopathy who would serve as the study group. Sympathetic Nerve Activity; Mental StrCold Pressor Testess Test (Color Word Test); The Modified Oxford Technique for Baroreflex Sensitivity; Cold Pressor Test; Echocardiographic evaluation | Device: Sympathetic Nerve Activity<br>* Resting Sympathetic Nerve Activity<br>Behavioral: Mental Stress Test (Color Word Test)<br>* 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.<br>Drug: The Modified Oxford Technique for Baroreflex Sensitivity<br>* 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.<br>* Other names: Phenylephrine hydrochloride;Other: Cold Pressor Test<br>* 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.<br>Device: Echocardiographic evaluation<br>* 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.<br>|
| Active Comparator: Control<br>Control subjects will be age and sex matched otherwise healthy people with no prior cardiac disease or other severe medical conditions. Sympathetic Nerve Activity; Mental Stress Test (Color Word Test); The Modified Oxford Technique for Baroreflex Sensitivity; Cold Pressor Test; Echocardiographic evaluation | Device: Sympathetic Nerve Activity<br>* Resting Sympathetic Nerve Activity<br>Behavioral: Mental Stress Test (Color Word Test)<br>* 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.<br>Drug: The Modified Oxford Technique for Baroreflex Sensitivity<br>* 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.<br>* Other names: Phenylephrine hydrochloride;Other: Cold Pressor Test<br>* 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.<br>Device: Echocardiographic evaluation<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identifying Risk Factors and Developing Strategies to Prevent the Occurrence of Stress Cardiomyopathy in Situations Where the Likelihood in Susceptible Individuals May be High. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stress-induced cardiomyopathy, Takotsubo cardiomyopathy