Cardiomyopathy, HypertrophicNCT00074880
The Role of Heart Stiff and Weak Atrium on Exercise Capacity in Patients With Hypertrophic Cardiomyopathy
An observational study of Cardiomyopathy, Hypertrophic, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
This study will examine how heart stiffness and a weak atrium affect exercise capacity and symptoms in patients with hypertrophic cardiomyopathy (HCM). The atrium is the booster pumping chamber of the heart that helps the ventricle (main pumping chamber), to fill properly. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cardiomyopathy, Hypertrophic
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2003to Mar 2005
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HCM defined as maximal LV wall thickness by echocardiography greater than 13mm in the absence of other causes of LVH or greater than 15mm asymmetrical LV wall thickness if there is a history of mild hypertension (defined as systolic less than 160mmHg and diastolic less than 100mHg) controlled for greater than 6 months
- Non-obstructive HCM
- Age greater than or equal to 21 years.
- Patients with LV obstruction treated by LV myotomy and myectomy or percutaneous septal alcohol ablation that meet inclusion criteria are eligible for this study.
Who cannot join
- LV outflow obstruction noted during Doppler echocardiography at rest or with Valsalva maneuver defined as instantaneous peak gradient greater than 30 mmHg
- Hemodynamically significant valvular disorders, history of significant coronary obstruction (greater than 50% in any single artery), angina symptoms, myocardial ischemia on an imaging stress test or evidence of prior myocardial infarction. Patients older than 40 years of age with effort induced anginal symptoms typical of coronary insufficiency and a coronary distribution of myocardial ischemia on an imaging stress test will be considered for the study if coronary angiography rules out significant obstructive coronary disease.
- Chronic atrial fibrillation
- Cardiac pacemaker or other metallic implant unsafe for MRI
- Uncontrolled hypertension
- Dependence on a beta blocker that cannot be withdrawn
Show all 16Show fewer
- Dependence on a calcium blocker that cannot be withdrawn
- Current use of digoxin
- History of digitalis intolerance
- Renal failure
- Diabetes mellitus
- Pregnancy or lactation
- Failure to indicate effective method of birth control measures if female patient is of childbearing age.
- Inability to exercise or disease states likely to result in impaired exercise capacity (such as pulmonary, hematological and musculoskeletal disorders)
- Echocardiographic images of insufficient quality, even after administration of contrast agent, for volumetric analysis.
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: The Role of Atrio-Ventricular Coupling in Exercise Tolerance in Non-Obstructive Hypertrophic Cardiomyopathy
This study will examine how heart stiffness and a weak atrium affect exercise capacity and symptoms in patients with hypertrophic cardiomyopathy (HCM). The atrium is the booster pumping chamber of the heart that helps the ventricle (main pumping chamber), to fill properly. HCM is an inherited disease in which the ventricle becomes thickened and, in some patients, stiff. The stiffness makes it difficult for the ventricle to fill and empty, causing breathing difficulty, fatigue, and reduced exercise capacity. Scar formation and a weakened atrium can cause the heart to stiffen. Information gained from this study may guide doctors in prescribing medicines to reduce scarring or improve atrial function.
Patients 21 years of age and older with hypertrophic cardiomyopathy may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram (EKG), blood tests, Holter monitor, and echocardiogram. A Holter monitor is a device about the size of a Walkman that is connected to three wires that are attached to the chest. It is worn for 24 hours to provide continuous monitoring of heart rhythm. An echocardiogram uses a small probe that emits sound waves to produce images of the heart. The probe is moved across the chest and the reflection of the sound waves from the chambers of the heart produce images showing the heart's thickness and function.
Read more
Participants will undergo the following tests and procedures over 3 days:
- Physical examination and echocardiogram.
- Intravenous cannula insertion: A plastic tube is inserted into an arm vein for collecting blood samples to measure substances that the heart and circulatory system release at rest and during exercise.
- Impedance cardiography: A small current of electricity is passed across the chest and electrodes similar to those used for an EKG test are placed to measure blood flow in the area of the current.
- Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein either in the arm, under the collarbone, or in the neck and advanced to the right atrium and ventricle. The catheter remains in place during the echocardiogram tilt and bicycle exercise tests (see below).
- Echocardiogram tilt test: The patient lies flat on a table. After a few minutes, the table is tilted so that the patient's head is just above his or her feet for a short while, then is positioned flat again, and then tilted so the feet are just above the head. Echocardiographic measurements and blood samples are taken at intervals to examine heart function during changes in posture.
- Echocardiogram bicycle stress test: The patient exercises for as long as possible on a bicycle-like machine while lying on his or her back. Echocardiographic measurements and blood samples are taken at intervals during the test.
- Treadmill stress test: The patient runs for as long as possible on a treadmill that increases in difficulty. The patient wears a facemask or mouthpiece through which small amounts of gases are added in order to measure the ability of the heart and lung to increase their effectiveness with exercise.
- Digoxin loading: Only patients who demonstrate limited exercise capacity and for whom digoxin is not a risk will undergo this procedure. A medicine that makes the heart contract more strongly, digoxin is used to treat certain heart abnormalities. Patients are given doses of either digoxin or placebo (a look-alike injection with no active ingredient) at 4-hour intervals over a 24-hour period and then repeat the tilt test and the bicycle and treadmill exercise tests
Read the detailed description
Primary hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by thickening (hypertrophy) of the left ventricular (LV) wall, dyspnea and/or fatigue in the setting of a normal or supra-normal LV ejection fraction. The specific mechanisms underlying heart failure-related symptomatology in non-obstructive HCM are poorly defined, but as the vast majority of HCM patients with heart failure have apparently preserved LV contractile function, their symptoms of dyspnea and fatigue are presumed due to perturbations of the relaxation/filling phase (diastole) of the cardiac cycle, which has been termed "diastolic dysfunction". In fact, diastole is mechanistically complex and involves LV pressure decay (relaxation), chamber compliance and atrial contractile function. LV end-diastolic volume, which represents fiber stretch, governs LV contractile function and stroke volume via the Frank-Starling mechanism. End-diastolic fiber stretch is, in turn, dependent on late diastolic filling due to atrial ejection. This atrial "booster pump" is load-dependent and also responsive to inotropic effect. The interaction of atrial inotropic reserve, LV end-diastolic pressure (atrial afterload) and LV compliance (which mediates LV end-diastolic pressure and volume) may be generically considered as "atrio-ventricular coupling" which, in theory, should be at least partially responsible for modulations in exercise-induced augmentation of cardiac output related to enhancement of LV end-diastolic volume or "preload reserve". Previous studies have suggested that limitations of preload reserve may explain exercise-associated symptoms of congestive heart failure. The potential ability of new technologies to accurately assess atrio-ventricular coupling as it relates to preload reserve present opportunities for investigation into mechanisms of heart failure operative in patients with stiff left ventricles with intact systolic function. Elucidation of these previously unapproachable mechanisms may be important in targeting therapy and the design and analysis of future interventional trials.
In this pilot study, we hypothesize that exercise intolerance in HCM patients is due to limited LV preload-reserve which, in turn, is mediated by disequilibrium of atrio-ventricular coupling and, possibly, limitations in atrial inotropic reserve. We will test novel analytic tools, including measures of LV compliance and load-independent atrial systolic fuction (atrial systolic elastance), in attempts to dissect out the components of atrio-ventricular coupling which underly HCM-associated symptoms and reduced preload reserve. Further, we will assess serum and cardiac MRI markers of myocardial fibrosis to determine the effect of collagen remodeling on LV relaxation, compliance and atrial afterload. Finally, we will examine the effects of short-term cardiac glycoside (inotropic) therapy on atrial systolic elastance, preload reserve and exercise tolerance. The results of this investigation will be implemented in the design of subsequent interventional protocols targeted towards mechanisms of the stiff heart syndrome.
- Conditions
- Cardiomyopathy, Hypertrophic
- Keywords
- Cardiac Hypertrophy, Diastolic Dysfunction, Cardiac Glycosides, Cardiac Fibrosis, Atrial Systole
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Cardiomegaly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2003 (estimated)
- Study startDec 2003
- Study completionMar 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cardiomyopathy, HypertrophicStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 50 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00074880
- Sponsor's protocol ID
- 040062
- Other IDs
- 04-H-0062
- Status last verified
- Mar 2005
- First submitted
- 22 Dec 2003
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Blauvelt A, Katz SI, Udey MC. Human Langerhans cells express E-cadherin. J Invest Dermatol. 1995 Feb;104(2):293-6. doi: 10.1111/1523-1747.ep12612830.
PubMed 7829887Blauvelt A, Clerici M, Lucey DR, Steinberg SM, Yarchoan R, Walker R, Shearer GM, Katz SI. Functional studies of epidermal Langerhans cells and blood monocytes in HIV-infected persons. J Immunol. 1995 Apr 1;154(7):3506-15.
PubMed 7897231Enk CD, Sredni D, Blauvelt A, Katz SI. Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro. J Immunol. 1995 May 1;154(9):4851-6.
PubMed 7722334
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Atrio-Ventricular Coupling in Exercise Tolerance in Non-Obstructive Hypertrophic Cardiomyopathy
- ClinicalTrials.gov ID
- NCT00074880
- Acronym / sponsor ID
- 040062
- Conditions
- Cardiomyopathy, Hypertrophic
- Keywords
- Cardiac Hypertrophy, Diastolic Dysfunction, Cardiac Glycosides, Cardiac Fibrosis, Atrial Systole
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Dec 2003
- Study completion
- Mar 2005
- First posted
- 23 Dec 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine how heart stiffness and a weak atrium affect exercise capacity and symptoms in patients with hypertrophic cardiomyopathy (HCM). The atrium is the booster pumping chamber of the heart that helps the ventricle (main pumping chamber), to fill properly. HCM is an inherited disease in which the ventricle becomes thickened and, in some patients, stiff. The stiffness makes it difficult for the ventricle to fill and empty, causing breathing difficulty, fatigue, and reduced exercise capacity. Scar formation and a weakened atrium can cause the heart to stiffen. Information gained from this study may guide doctors in prescribing medicines to reduce scarring or improve atrial function.
Patients 21 years of age and older with hypertrophic cardiomyopathy may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram (EKG), blood tests, Holter monitor, and echocardiogram. A Holter monitor is a device about the size of a Walkman that is connected to three wires that are attached to the chest. It is worn for 24 hours to provide continuous monitoring of heart rhythm. An echocardiogram uses a small probe that emits sound waves to produce images of the heart. The probe is moved across the chest and the reflection of the sound waves from the chambers of the heart produce images showing the heart's thickness and function.
Participants will undergo the following tests and procedures over 3 days:
- Physical examination and echocardiogram.
- Intravenous cannula insertion: A plastic tube is inserted into an arm vein for collecting blood samples to measure substances that the heart and circulatory system release at rest and during exercise.
- Impedance cardiography: A small current of electricity is passed across the chest and electrodes similar to those used for an EKG test are placed to measure blood flow in the area of the current.
- Pulmonary artery catheterization: A catheter (plastic tube) is inserted into a vein either in the arm, under the collarbone, or in the neck and advanced to the right atrium and ventricle. The catheter remains in place during the echocardiogram tilt and bicycle exercise tests (see below).
- Echocardiogram tilt test: The patient lies flat on a table. After a few minutes, the table is tilted so that the patient's head is just above his or her feet for a short while, then is positioned flat again, and then tilted so the feet are just above the head. Echocardiographic measurements and blood samples are taken at intervals to examine heart function during changes in posture.
- Echocardiogram bicycle stress test: The patient exercises for as long as possible on a bicycle-like machine while lying on his or her back. Echocardiographic measurements and blood samples are taken at intervals during the test.
- Treadmill stress test: The patient runs for as long as possible on a treadmill that increases in difficulty. The patient wears a facemask or mouthpiece through which small amounts of gases are added in order to measure the ability of the heart and lung to increase their effectiveness with exercise.
- Digoxin loading: Only patients who demonstrate limited exercise capacity and for whom digoxin is not a risk will undergo this procedure. A medicine that makes the heart contract more strongly, digoxin is used to treat certain heart abnormalities. Patients are given doses of either digoxin or placebo (a look-alike injection with no active ingredient) at 4-hour intervals over a 24-hour period and then repeat the tilt test and the bicycle and treadmill exercise tests
Detailed description
Primary hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by thickening (hypertrophy) of the left ventricular (LV) wall, dyspnea and/or fatigue in the setting of a normal or supra-normal LV ejection fraction. The specific mechanisms underlying heart failure-related symptomatology in non-obstructive HCM are poorly defined, but as the vast majority of HCM patients with heart failure have apparently preserved LV contractile function, their symptoms of dyspnea and fatigue are presumed due to perturbations of the relaxation/filling phase (diastole) of the cardiac cycle, which has been termed "diastolic dysfunction". In fact, diastole is mechanistically complex and involves LV pressure decay (relaxation), chamber compliance and atrial contractile function. LV end-diastolic volume, which represents fiber stretch, governs LV contractile function and stroke volume via the Frank-Starling mechanism. End-diastolic fiber stretch is, in turn, dependent on late diastolic filling due to atrial ejection. This atrial "booster pump" is load-dependent and also responsive to inotropic effect. The interaction of atrial inotropic reserve, LV end-diastolic pressure (atrial afterload) and LV compliance (which mediates LV end-diastolic pressure and volume) may be generically considered as "atrio-ventricular coupling" which, in theory, should be at least partially responsible for modulations in exercise-induced augmentation of cardiac output related to enhancement of LV end-diastolic volume or "preload reserve". Previous studies have suggested that limitations of preload reserve may explain exercise-associated symptoms of congestive heart failure. The potential ability of new technologies to accurately assess atrio-ventricular coupling as it relates to preload reserve present opportunities for investigation into mechanisms of heart failure operative in patients with stiff left ventricles with intact systolic function. Elucidation of these previously unapproachable mechanisms may be important in targeting therapy and the design and analysis of future interventional trials.
In this pilot study, we hypothesize that exercise intolerance in HCM patients is due to limited LV preload-reserve which, in turn, is mediated by disequilibrium of atrio-ventricular coupling and, possibly, limitations in atrial inotropic reserve. We will test novel analytic tools, including measures of LV compliance and load-independent atrial systolic fuction (atrial systolic elastance), in attempts to dissect out the components of atrio-ventricular coupling which underly HCM-associated symptoms and reduced preload reserve. Further, we will assess serum and cardiac MRI markers of myocardial fibrosis to determine the effect of collagen remodeling on LV relaxation, compliance and atrial afterload. Finally, we will examine the effects of short-term cardiac glycoside (inotropic) therapy on atrial systolic elastance, preload reserve and exercise tolerance. The results of this investigation will be implemented in the design of subsequent interventional protocols targeted towards mechanisms of the stiff heart syndrome.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- HCM defined as maximal LV wall thickness by echocardiography greater than 13mm in the absence of other causes of LVH or greater than 15mm asymmetrical LV wall thickness if there is a history of mild hypertension (defined as systolic less than 160mmHg and diastolic less than 100mHg) controlled for greater than 6 months
- Non-obstructive HCM
- Age greater than or equal to 21 years.
- Patients with LV obstruction treated by LV myotomy and myectomy or percutaneous septal alcohol ablation that meet inclusion criteria are eligible for this study.
Key exclusion criteria (16 listed)
- LV outflow obstruction noted during Doppler echocardiography at rest or with Valsalva maneuver defined as instantaneous peak gradient greater than 30 mmHg
- Hemodynamically significant valvular disorders, history of significant coronary obstruction (greater than 50% in any single artery), angina symptoms, myocardial ischemia on an imaging stress test or evidence of prior myocardial infarction. Patients older than 40 years of age with effort induced anginal symptoms typical of coronary insufficiency and a coronary distribution of myocardial ischemia on an imaging stress test will be considered for the study if coronary angiography rules out significant obstructive coronary disease.
- Chronic atrial fibrillation
- Cardiac pacemaker or other metallic implant unsafe for MRI
- Uncontrolled hypertension
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7829887Blauvelt A, Katz SI, Udey MC. Human Langerhans cells express E-cadherin. J Invest Dermatol. 1995 Feb;104(2):293-6. doi: 10.1111/1523-1747.ep12612830.
- Background: PubMed 7897231Blauvelt A, Clerici M, Lucey DR, Steinberg SM, Yarchoan R, Walker R, Shearer GM, Katz SI. Functional studies of epidermal Langerhans cells and blood monocytes in HIV-infected persons. J Immunol. 1995 Apr 1;154(7):3506-15.
- Background: PubMed 7722334Enk CD, Sredni D, Blauvelt A, Katz SI. Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro. J Immunol. 1995 May 1;154(9):4851-6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiomyopathy, Hypertrophic, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00074880, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.