Characterization of Sympathetic Nerve Activity in Stress Cardiomyopathy

• ClinicalTrials.gov Identifier: NCT01048125
• Recruitment Status: Terminated
• First Posted: January 13, 2010
• Results First Posted: November 23, 2016
• Last Update Posted: November 23, 2016
• Sponsor: University of Missouri-Columbia
• Information provided by (Responsible Party): Anand Chockalingam, University of Missouri-Columbia

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiomyopathy	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	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Characterization of Sympathetic Nerve Activity in Stress Cardiomyopathy
• Study Start Date: August 2009
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: July 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Study group; 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; 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 Names: Sodium Nitroprusside; Phenylephrine hydrochloride; 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.
Active Comparator: Control; 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; 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 Names: Sodium Nitroprusside; Phenylephrine hydrochloride; 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.

Outcome Measures

Primary Outcome Measures :

1. Identifying Risk Factors and Developing Strategies to Prevent the Occurrence of Stress Cardiomyopathy in Situations Where the Likelihood in Susceptible Individuals May be High. [ Time Frame: 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Missouri

University of Missouri

Columbia, Missouri, United States, 65212

Sponsors and Collaborators

University of Missouri-Columbia

Investigators

• Principal Investigator: Anand Chockalingam, MD; University of Missouri-Columbia

More Information

• Responsible Party: Anand Chockalingam, Professor, Cardiology, University of Missouri-Columbia
• ClinicalTrials.gov Identifier: NCT01048125
• Other Study ID Numbers: 1141858
• First Posted: January 13, 2010
• Results First Posted: November 23, 2016
• Last Update Posted: November 23, 2016
• Last Verified: October 2016

Keywords provided by Anand Chockalingam, University of Missouri-Columbia:

Stress-induced cardiomyopathy; Takotsubo cardiomyopathy

Additional relevant MeSH terms:

Cardiomyopathies; Takotsubo Cardiomyopathy; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction; Nitroprusside; Phenylephrine; Oxymetazoline; Cardiotonic Agents; Mydriatics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Sympathomimetics; Vasoconstrictor Agents; Nasal Decongestants; Respiratory System Agents; Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Antihypertensive Agents; Vasodilator Agents; Nitric Oxide Donors