Hypertrophic Cardiomyopathy, Myocardial Fibrosis
Conditions
Keywords
Fibrosis, Hypertrophic cardiomyopathy, MRI, Myocardial Fibrosis, Spironolactone
Brief summary
Hypertrophic Cardiomyopathy (HCM) is the most common genetic cardiomyopathy and remains the leading cause of sudden cardiac death in young people and an important cause of heart failure symptoms and death at any age. In HCM, pathological remodeling of the left ventricle involving myocardial fibrosis is likely a major contributor to cardiac dysfunction and also a nidus for the generation of ventricular arrhythmias. Serum markers of collagen turnover have been shown to reliably reflect the magnitude of myocardial fibrosis in a variety of cardiovascular diseases. In addition, aldosterone antagonist drugs have been shown to decrease fibrous tissue formation in the myocardium in certain pathologic cardiovascular states in which aldosterone production is increased. In HCM, aldosterone production is up-regulated and has been implicated in the formation of myocardial fibrosis. Therefore, the specific aims of this proposal are to: 1. assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters 2. examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters. 3. explore the effects of a 12-month treatment with aldosterone antagonist spironolactone on heart failure status, diastolic function, arrhythmic burden, and total LV mass and quantity of fibrosis by CMR. The results of this proposal will offer important insights into the clinical significance of myocardial fibrosis in this primary genetic cardiomyopathy. The demonstration that spironolactone decreases fibrosis and improves clinical course would provide the rational for a larger multicenter clinical trial evaluating this novel therapy for improving clinical outcome in patients with HCM.
Detailed description
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in the general population. Myocardial fibrosis has become a prominent and clinically relevant pathophysiologic component of this complex genetic disease, related to the risk for both sudden death and heart failure. For example, left ventricular replacement fibrosis and scarring has been implicated in triggering life threatening ventricular tachycardia/fibrillation and most recently has become a novel risk marker for sudden death, based on in vivo demonstration of extensive late gadolinium enhancement (LGE) with cardiovascular magnetic resonance (CMR). Extensive LGE identifies patients who benefit from primary prevention of sudden death with the implantable cardioverter-defibrillators (ICD), or who evolve to the end-stage of this disease with systolic dysfunction and consideration for heart transplant. The mineralocorticoid aldosterone has been shown to be a mediator of myocardial fibrosis, and blockade with spironolactone normalizes collagen content in HCM murine models. In addition, aldosterone antagonists have favorable clinical effects in patients with a variety of diseases associated with myocardial scarring such as congestive heart failure, systemic hypertension, and atherosclerotic coronary artery disease. However, it is uncertain whether spironolactone would have similar effects on the clinical and phenotypic expression of a genetic disease such as HCM. Therefore, we investigated whether mineralocorticoid receptor blockade with spironolactone would reduce measures reflecting myocardial fibrosis, producing favorable LV remodeling and ultimately leading to positive clinical effects for patients with HCM. The general aim of this study is to explore the role of fibrosis in HCM by testing the hypothesis that: the presence of magnitude of myocardial fibrosis bears clinical relevance for patients with HCM, and that mineralocorticoid receptor blockade will reduce myocardial fibrosis and thereby alter the natural history of the disease. Experimental design: prospective, randomized, double-blind, placebo-controlled trial in a consecutive HCM population at a single clinical center (Tufts Medical Center HCM Institution). Study procedures: HCM patients were recruited from Tufts Medical Center HCM Institution population from November 2007 to June 2009. Enrolled patients were randomized into two arms; treatment arm received 25mg at the start of study and then increased to target dose of 50mg if serum potassium was \<5.5mmol/L and serum creatinine-baseline creatinine was \<0.5mg/dl. This arm was then followed for 12 months. The control arm of the study received 25mg of placebo over 12 months. There was an additional control arm of age and gender-matched controls without HCM in the control arm to evaluate the serum markers of collagen turnover at baseline. These controls had a one time blood draw of 15mL (3 teaspoons) to assess serum biomarkers of interest and were not be followed for 12 months. Specific outcome measures: Primary Outcome: examine the effects of a 12-month treatment with the aldosterone antagonist spironolactone on magnitude of fibrosis as measured by serum markers of collagen turnover as well as changes in clinical and morphologic disease parameters. Secondary Outcomes: explore the effects of a 12-month treatment with aldosterone antagonist spironolactone on heart failure status, diastolic function, arrhythmic burden, and total LV mass and quantity of fibrosis by CMR. Secondary Outcome: assess serum markers of collagen turnover at baseline and correlate these findings with a variety of clinical and morphologic disease parameters
Interventions
DRUGSpironolactone
spironolactone 50mg daily
DRUGPlacebo
inactive placebo pill daily
Sponsors
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Hypertrophic cardiomyopathy 2. Able to swallow pills 3. No prior septal reduction therapy 4. Negative serum or hCG pregnancy test
Exclusion criteria
1. Unable or unwilling to perform treadmill cardiopulmonary exercise test 2. Prior surgical myectomy or alcohol septal ablation 3. Known or suspected infiltrative or glycogen storage disease 4. Significant coronary artery disease, defined as atherosclerotic coronary artery narrowing \>70% of the luminal diameter by coronary angiography 5. Severe obstructive pulmonary disease, defined as forced expiratory volume in 1 second (FEV1) \<50% of predicted. 6. Prior intolerance or adverse reaction to aldosterone receptor antagonist. 7. History of hyper or hypoaldosteronism 8. Baseline serum potassium \>5.0 mmol/L. 9. Calculated creatinine clearance \<30 ml/min using Cockcroft-Gault formula. 10. Pregnant or breast feeding 11. Poorly controlled systemic hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, during 2 clinic visits. 12. Known conditions associated with elevated serum concentrations of PIIINP (e.g., chronic liver disease, diabetes mellitus, tumors, pulmonary fibrosis, bone and rheumatoid diseases, extensive wounds) or PINP (e.g., alcoholic liver disease, metabolic bone disease, thyroid disorders), including recent trauma (≤2 weeks) or surgery (≤6 months) 13. Taking drugs known to directly influence collagen metabolism including, amiodorone, ACE or angiotensin II inhibitors, aldosterone antagonists, statins, glucocorticoids and estrogens 14. Patients with ICDs/pacemakers will be recruited in the study, but will be excluded from the CMR component.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | The time points measured were at Baseline and at 12 Months (Follow-Up). | Specific variables of collagen turnover markers that will be evaluated include markers of collagen synthesis (PINP, PIIINP), and marker of collagen degradation (ICTP). A two-sample t-test was used to compare the differences between these collagen turnover markers at baseline and the absolute differences in change from baseline to 12 months of follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class | Time points were measured at Baseline and again at 12 months (follow-up) | This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to assess heart failure symptoms according to the New York Heart Association (NYHA) functional class, which is an estimate of a patients functional ability. The NYHA functional classes include: Class I (no limitation of physical activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity), and Class IV (unable to carry out any physical acitivity without discomfort). |
| Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e') | The time points measured were at Baseline and at 12 Months (Follow-Up). | This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to measure indices of diastolic function by Tissue Doppler Echocardiography using the Septal E/e' ratio. |
| Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV) | The time points measured were at Baseline and at 12 Months (Follow-Up). | CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\^2), and left atrial dimension (in mm). |
| Measure of Functional Capacity: Peak Oxygen Consumption With Exercise | The time points measured were at Baseline and at 12 Months (Follow-Up). | This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to determine if spironolactone improves a subject's functional capacity during exercise (peak oxygen consumption levels/peak VO2). Peak VO2 levels were measured in ml/kg/min. |
| Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2) | The time points measured were at Baseline and at 12 Months (Follow-Up) | CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic (LVED) cavity size (in mm/m\^2), and left atrial dimension (in mm). |
| Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm) | The time points measured were at Baseline and at 12 Months (Follow-Up) | CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\^2), and left atrial dimension (in mm). |
| Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm) | The time points measured were at Baseline and at 12 Months (Follow-Up). | CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\^2), and left atrial dimension (in mm). |
Countries
United States
Participant flow
Recruitment details
Subjects diagnosed with HCM, between the ages of 18-55 (male or female), who are not pregnant were recruited from the Tufts Medical Center Hypertrophic Cardiomyopathy Center. The last patient completed the study in August of 2012.
Participants by arm
| Arm | Count |
|---|---|
| Spironolactone spironolactone: spironolactone 50mg daily | 26 |
| Placebo spironolactone: spironolactone 50mg daily | 27 |
| Total | 53 |
Baseline characteristics
| Characteristic | Spironolactone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40 years STANDARD_DEVIATION 13 | 42 years STANDARD_DEVIATION 13 | 41 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 26 Participants | 27 Participants | 53 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 27 |
| other Total, other adverse events | 0 / 26 | 0 / 27 |
| serious Total, serious adverse events | 0 / 26 | 0 / 27 |
Outcome results
Primary
Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo.
Specific variables of collagen turnover markers that will be evaluated include markers of collagen synthesis (PINP, PIIINP), and marker of collagen degradation (ICTP). A two-sample t-test was used to compare the differences between these collagen turnover markers at baseline and the absolute differences in change from baseline to 12 months of follow-up.
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up).
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | Baseline (PINP) | 2.1 micrograms/L | Standard Deviation 1 |
| Spironolactone | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | 12 Months (PINP) | 0.7 micrograms/L | Standard Deviation 12 |
| Spironolactone | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | Baseline (PIIINP) | 4.7 micrograms/L | Standard Deviation 2 |
| Spironolactone | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | 12 Months (PIIINP) | 2.0 micrograms/L | Standard Deviation 0.8 |
| Spironolactone | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | Baseline (ICTP) | 2.2 micrograms/L | Standard Deviation 1.4 |
| Spironolactone | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | 12 Months (ICTP) | 2.7 micrograms/L | Standard Deviation 1.4 |
| Placebo Control | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | Baseline (ICTP) | 2.5 micrograms/L | Standard Deviation 1.4 |
| Placebo Control | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | Baseline (PINP) | 2.1 micrograms/L | Standard Deviation 1.2 |
| Placebo Control | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | 12 Months (PIIINP) | 1.6 micrograms/L | Standard Deviation 0.8 |
| Placebo Control | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | 12 Months (PINP) | 0.6 micrograms/L | Standard Deviation 1.3 |
| Placebo Control | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | 12 Months (ICTP) | -2.3 micrograms/L | Standard Deviation 1.4 |
| Placebo Control | Absolute Change in Serum Markers of Collagen Turnover (Micrograms/L) Over a One-year Follow-up Period in the Spironolactone Group Compared to Placebo. | Baseline (PIIINP) | 4.5 micrograms/L | Standard Deviation 2.5 |
Comparison: A two-sample T-test was used to compare continuous variable PINP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups at baseline.p-value: 1t-test, 2 sided
Comparison: A two-sample T-test was used to compare continuous variable PIIINP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups at baseline.p-value: 0.8t-test, 2 sided
Comparison: A two-sample T-test was used to compare continuous variable ICTP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups at baseline.p-value: 0.3t-test, 2 sided
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable PINP (serum marker of collagen formation/degradation) between spironolactone treated and placebo groups.p-value: 1t-test, 2 sided
Secondary
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm)
CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\^2), and left atrial dimension (in mm).
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up)
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm) | Left Atrial Dimension (Baseline) | 40 millimeters | Standard Deviation 6 |
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm) | Left Atrial Dimension (12-Month Follow-Up) | 40 millimeters | Standard Deviation 5 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm) | Left Atrial Dimension (Baseline) | 41 millimeters | Standard Deviation 5 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Atrial Dimension (in mm) | Left Atrial Dimension (12-Month Follow-Up) | 40 millimeters | Standard Deviation 6 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable left atrial dimension between spironolactone treated and placebo groups.p-value: 0.8t-test, 2 sided
Secondary
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2)
CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic (LVED) cavity size (in mm/m\^2), and left atrial dimension (in mm).
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up)
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2) | LVED Cavity Size (Baseline) | 133 mm/m^2 | Standard Deviation 26 |
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2) | LVED Cavity Size (12-Month Follow-Up) | 129 mm/m^2 | Standard Deviation 29 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2) | LVED Cavity Size (Baseline) | 145 mm/m^2 | Standard Deviation 46 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Left Ventricular End-Diastolic (LVED) Cavity Size (in mm/m^2) | LVED Cavity Size (12-Month Follow-Up) | 146 mm/m^2 | Standard Deviation 44 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable left ventricular end-diastolic (LVED) cavity size between spironolactone treated and placebo groups.p-value: 0.7t-test, 2 sided
Secondary
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm)
CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\^2), and left atrial dimension (in mm).
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up).
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm) | Maximum Left Ventricular Wall Thickness (Baseline) | 22 millimeters | Standard Deviation 7 |
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm) | Maximum Left Ventricular Wall Thickness (12-Month Follow-Up) | 22 millimeters | Standard Deviation 6 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm) | Maximum Left Ventricular Wall Thickness (Baseline) | 21 millimeters | Standard Deviation 6 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Maximum Left Ventricular Wall Thickness (in mm) | Maximum Left Ventricular Wall Thickness (12-Month Follow-Up) | 19 millimeters | Standard Deviation 3 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable maximum left ventricular wall thickness (Max LV) between spironolactone treated and placebo groups.p-value: 0.4t-test, 2 sided
Secondary
Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV)
CMR will be utilized as it has superior reproducibility (as compared to 2-D echocardiography). Late Gadolinium Enhancement (LGE) Assessment of myocardial fibrosis by CMR will be expressed as a percentage of left ventricular mass (%LV), maximum left ventricular wall thickness (in mm), left ventricular end-diastolic cavity size (in mm/m\^2), and left atrial dimension (in mm).
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up).
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV) | LGE Assessment of Myocardial Fibrosis (Baseline) | 1.1 Percentage of Total LV Mass | Standard Deviation 2.5 |
| Spironolactone | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV) | LGE Assessment of Myocardial Fibrosis (12-Month Follow-Up) | 1.8 Percentage of Total LV Mass | Standard Deviation 2.9 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV) | LGE Assessment of Myocardial Fibrosis (Baseline) | 2.5 Percentage of Total LV Mass | Standard Deviation 3.3 |
| Placebo Control | Assessment of Cardiac Mass and Fibrosis by Cardiac Magnetic Resonance Imaging (CMR) - Percentage of Left Ventricular Mass (%LV) | LGE Assessment of Myocardial Fibrosis (12-Month Follow-Up) | 2.8 Percentage of Total LV Mass | Standard Deviation 4.1 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable percentage of left ventricular mass (%LV) between spironolactone treated and placebo groups.p-value: 0.7t-test, 2 sided
Secondary
Measure of Functional Capacity: Peak Oxygen Consumption With Exercise
This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to determine if spironolactone improves a subject's functional capacity during exercise (peak oxygen consumption levels/peak VO2). Peak VO2 levels were measured in ml/kg/min.
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up).
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Measure of Functional Capacity: Peak Oxygen Consumption With Exercise | Peak VO2 (Baseline) | 30 ml/kg/min | Standard Deviation 7 |
| Spironolactone | Measure of Functional Capacity: Peak Oxygen Consumption With Exercise | Peak VO2 (12-Month Follow-Up) | 29 ml/kg/min | Standard Deviation 8 |
| Placebo Control | Measure of Functional Capacity: Peak Oxygen Consumption With Exercise | Peak VO2 (Baseline) | 28 ml/kg/min | Standard Deviation 7 |
| Placebo Control | Measure of Functional Capacity: Peak Oxygen Consumption With Exercise | Peak VO2 (12-Month Follow-Up) | 29 ml/kg/min | Standard Deviation 6 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable peak oxygen consumption with exercise (peak VO2) between spironolactone treated and placebo groups.p-value: 0.7t-test, 2 sided
Secondary
Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class
This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to assess heart failure symptoms according to the New York Heart Association (NYHA) functional class, which is an estimate of a patients functional ability. The NYHA functional classes include: Class I (no limitation of physical activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity), and Class IV (unable to carry out any physical acitivity without discomfort).
Time frame: Time points were measured at Baseline and again at 12 months (follow-up)
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class | NYHA Class (Baseline) | 1.6 score on a scale | Standard Deviation 0.7 |
| Spironolactone | Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class | NYHA Class (12-Month Follow Up) | 1.7 score on a scale | Standard Deviation 0.8 |
| Placebo Control | Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class | NYHA Class (Baseline) | 1.5 score on a scale | Standard Deviation 0.6 |
| Placebo Control | Measure of Heart Failure Symptoms According to the New York Heart Association Functional Class | NYHA Class (12-Month Follow Up) | 1.6 score on a scale | Standard Deviation 0.7 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable New York Heart Association (NYHA) Functional Class between spironolactone treated and placebo groups.p-value: 0.8t-test, 2 sided
Secondary
Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e')
This data was collected at baseline, prior to drug administration, and again at 12-months of follow-up to measure indices of diastolic function by Tissue Doppler Echocardiography using the Septal E/e' ratio.
Time frame: The time points measured were at Baseline and at 12 Months (Follow-Up).
Population: 53 HCM patients (41 +/- 13 years old, 72% male) were randomized; demographic, clinical, and structural variables were well matched at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spironolactone | Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e') | Diastolic Function (Baseline) | 14 Ratio | Standard Deviation 4 |
| Spironolactone | Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e') | Diastolic Function (12-month Follow-Up) | 13 Ratio | Standard Deviation 6 |
| Placebo Control | Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e') | Diastolic Function (Baseline) | 15 Ratio | Standard Deviation 7 |
| Placebo Control | Measure of Indices of Diastolic Function by Tissue Doppler Echocardiography (Septal E/e') | Diastolic Function (12-month Follow-Up) | 13 Ratio | Standard Deviation 4 |
Comparison: A two-sample T-test was used to compare the absolute differences in change from baseline to 12 months in continuous variable Septal E/e' between spironolactone treated and placebo groups.p-value: 1t-test, 2 sided