Heart Failure With Preserved Ejection Fraction, Transthyretin Amyloid Cardiomyopathy
Conditions
Keywords
prevalence, transthyretin amyloid, ATTR-CM, HFpEF, scintigraphy
Brief summary
This study is a global, multi-center study designed to estimate the global prevalence of transthyretin amyloid cardiomyopathy (ATTR-CM) within a clinically at risk population \[participants with heart failure with preserved ejection fraction (HFpEF)\].
Interventions
DIAGNOSTIC_TESTScintigraphy
scintigraphy
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Intervention model description
To determine global prevalence of transthyretin amyloid cardiomyopathy in participants diagnosed with heart failure with preserved ejection fraction. No study treatment will be dispensed however, participants will undergo scintigraphy.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Medical history of heart failure (HF) with: 1. At least 1 episode with clinical evidence of HF (without hospitalization) by signs or symptoms of volume overload or elevated intracardiac pressures that required/requires treatment with a diuretic for improvement; OR 2. 1 prior hospitalization for HF. 2. Left ventricular ejection fraction (LVEF) \>40%. 3. End-diastolic interventricular septal wall thickness (IVST) ≥12 mm. 4. Willing and able to undergo scintigraphy.
Exclusion criteria
1. Diagnosis of heart failure with reduced ejection fraction (HFrEF) (EF ≤40%). 2. Prior clinical history of myocardial infarction, CABG or multi-vessel obstructive coronary disease (\>50% stenosis of ≥2 epicardial coronary arteries). 3. Presence or history of any severe valvular heart disease (obstructive or regurgitant). 4. A confirmed diagnosis of a non-amyloid infiltrative cardiomyopathy (ie, cardiac sarcoidosis, hemochromatosis), muscular dystrophies, cardiomyopathy with reversible causes, hypertrophic obstructive cardiomyopathy with known genetic etiology, or known pericardial constriction. 5. Any type of diagnosed amyloidosis (eg, amyloid A amyloidosis, primary \[light chain\] amyloidosis) or prior diagnosis of ATTR-CM. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Prevalence of ATTR-CM in HFpEF Participants Clinically At-Risk of Disease Among Total Evaluable Participants | Day 1 | Global prevalence of ATTR-CM in HFpEF participants was obtained by dividing the number of participants who were diagnosed with ATTR-CM in the study by the total number of HFpEF participants evaluated. Diagnosis of ATTR-CM was defined as: cardiac scintigraphy Grade 1, with confirmation of ATTR by cardiac biopsy; or cardiac scintigraphy Grade 2 or above. Exact 95% confidence intervals for the prevalence estimates were calculated using the method of Clopper and Pearson. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Day 1 | The prevalence of ATTR-CM in HFpEF participants was evaluated for subgroups including regions (North America, Europe, and Asia), age categories (60-64 years, 65-69 years, 70-74 years, 75-79 years, 80-85 years, 85-89 years, \>=90 years), and gender (male, female). The estimate of prevalence was defined as the number of participants meeting the diagnosis criteria of ATTR-CM divided by the number of evaluable participants in the study in the given subgroup category. Diagnosis of ATTR-CM was defined as: cardiac scintigraphy Grade 1, with confirmation of ATTR by cardiac biopsy; or cardiac scintigraphy Grade 2 or above. Exact 95% confidence intervals for the prevalence estimates were calculated using the method of Clopper and Pearson. |
| Number of Participants According to TTR Genotypes Among Participants Diagnosed With ATTR-CM | Day 1 | Number of participants diagnosed with ATTR-CM were evaluated for TTR genotypes (wild-type or hereditary form). |
| Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | Day 1 | Participants were evaluated using the NYHA classification at Day 1. Class I: participants with cardiac disease but without resulting limitations of physical activity. Class II: participants with cardiac disease resulting in slight limitation of physical activity. Class III: participants with cardiac disease resulting in marked limitation of physical activity. Class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. |
| N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) in Participants With and Without ATTR-CM | Day 1 | Participants were evaluated using NT-proBNP cardiac biomarker that was assessed at Day 1. |
Countries
Canada, France, Italy, Japan, Poland, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 347 heart failure with preserved ejection fraction (HFpEF) participants within a clinically at-risk population were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Participants With ATTR-CM Participants enrolled in the study who were positive for transthyretin amyloid cardiomyopathy (ATTR-CM) by scintigraphy and were evaluable. | 56 |
| Participants Without ATTR-CM Participants enrolled in the study who were negative for ATTR-CM by scintigraphy and were evaluable. | 259 |
| Non-evaluable Participants Participants enrolled in the study who were non-evaluable. | 32 |
| Total | 347 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 28 |
| Overall Study | Study terminated by sponsor | 23 | 7 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Participants With ATTR-CM | Participants Without ATTR-CM | Non-evaluable Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 84.13 Years STANDARD_DEVIATION 6.64 | 76.52 Years STANDARD_DEVIATION 7.87 | 75.56 Years STANDARD_DEVIATION 7.51 | 77.66 Years STANDARD_DEVIATION 8.15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 99 Participants | 9 Participants | 130 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 158 Participants | 23 Participants | 214 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 20 Participants | 1 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 11 Participants | 6 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 48 Participants | 226 Participants | 25 Participants | 299 Participants |
| Sex: Female, Male Female | 14 Participants | 129 Participants | 21 Participants | 164 Participants |
| Sex: Female, Male Male | 42 Participants | 130 Participants | 11 Participants | 183 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 56 | 1 / 259 | 0 / 32 |
| other Total, other adverse events | 11 / 56 | 10 / 259 | 3 / 32 |
| serious Total, serious adverse events | 0 / 56 | 0 / 259 | 0 / 32 |
Outcome results
Primary
Global Prevalence of ATTR-CM in HFpEF Participants Clinically At-Risk of Disease Among Total Evaluable Participants
Global prevalence of ATTR-CM in HFpEF participants was obtained by dividing the number of participants who were diagnosed with ATTR-CM in the study by the total number of HFpEF participants evaluated. Diagnosis of ATTR-CM was defined as: cardiac scintigraphy Grade 1, with confirmation of ATTR by cardiac biopsy; or cardiac scintigraphy Grade 2 or above. Exact 95% confidence intervals for the prevalence estimates were calculated using the method of Clopper and Pearson.
Time frame: Day 1
Population: Evaluable analysis set included all participants who met the inclusion/exclusion criteria and completed Visit 1, excluding participants with cardiac scintigraphy assessed as non-evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants With HFpEF | Global Prevalence of ATTR-CM in HFpEF Participants Clinically At-Risk of Disease Among Total Evaluable Participants | 17.8 Percentage of participants |
Secondary
Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants
The prevalence of ATTR-CM in HFpEF participants was evaluated for subgroups including regions (North America, Europe, and Asia), age categories (60-64 years, 65-69 years, 70-74 years, 75-79 years, 80-85 years, 85-89 years, \>=90 years), and gender (male, female). The estimate of prevalence was defined as the number of participants meeting the diagnosis criteria of ATTR-CM divided by the number of evaluable participants in the study in the given subgroup category. Diagnosis of ATTR-CM was defined as: cardiac scintigraphy Grade 1, with confirmation of ATTR by cardiac biopsy; or cardiac scintigraphy Grade 2 or above. Exact 95% confidence intervals for the prevalence estimates were calculated using the method of Clopper and Pearson.
Time frame: Day 1
Population: Evaluable analysis set included all participants who met the inclusion/exclusion criteria and completed Visit 1, excluding participants with cardiac scintigraphy assessed as non-evaluable. Here, Number Analyzed signifies number of participants evaluable for specified rows of the arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Region: North America | 4.82 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Region: Europe | 23.81 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Region: Asia | 9.09 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: 60-64 years | 0 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: 65-69 years | 5.88 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: 70-74 years | 5.77 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: 75-79 years | 14.71 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: 80-84 years | 13.43 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: 85-89 years | 44.44 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Age: >=90 years | 42.11 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Gender: Female | 9.79 Percentage of participants |
| Participants With HFpEF | Global Prevalence of ATTR-CM in Participants With HFpEF Clinically At-Risk of Disease by Subgroups (Regions, Age, Gender) Among Total Evaluable Participants | Gender: Male | 24.42 Percentage of participants |
Secondary
N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) in Participants With and Without ATTR-CM
Participants were evaluated using NT-proBNP cardiac biomarker that was assessed at Day 1.
Time frame: Day 1
Population: Enrolled analysis set included all participants who met the inclusion/exclusion criteria and completed Visit 1. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants With HFpEF | N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) in Participants With and Without ATTR-CM | 2470.0 Nanogram per liter (ng/L) |
| Participants Without ATTR-CM | N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) in Participants With and Without ATTR-CM | 817.5 Nanogram per liter (ng/L) |
p-value: <0.0001Wilcoxon rank sum test
Secondary
Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification
Participants were evaluated using the NYHA classification at Day 1. Class I: participants with cardiac disease but without resulting limitations of physical activity. Class II: participants with cardiac disease resulting in slight limitation of physical activity. Class III: participants with cardiac disease resulting in marked limitation of physical activity. Class IV: participants with cardiac disease resulting in inability to carry on any physical activity without discomfort.
Time frame: Day 1
Population: Enrolled analysis set included all participants who met the inclusion/exclusion criteria and completed Visit 1.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With HFpEF | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class I | 2 Participants |
| Participants With HFpEF | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class II | 43 Participants |
| Participants With HFpEF | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class III | 8 Participants |
| Participants With HFpEF | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class IV | 3 Participants |
| Participants With HFpEF | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class I+II | 45 Participants |
| Participants With HFpEF | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class III+IV | 11 Participants |
| Participants Without ATTR-CM | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class I+II | 191 Participants |
| Participants Without ATTR-CM | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class I | 26 Participants |
| Participants Without ATTR-CM | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class IV | 2 Participants |
| Participants Without ATTR-CM | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class II | 165 Participants |
| Participants Without ATTR-CM | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class III+IV | 68 Participants |
| Participants Without ATTR-CM | Number of HFpEF Participants With and Without ATTR-CM Based on New York Heart Association (NYHA) Classification | NYHA Classification: Class III | 66 Participants |
p-value: 0.3006Chi-squared
Secondary
Number of Participants According to TTR Genotypes Among Participants Diagnosed With ATTR-CM
Number of participants diagnosed with ATTR-CM were evaluated for TTR genotypes (wild-type or hereditary form).
Time frame: Day 1
Population: Evaluable analysis set included all participants who met the inclusion/exclusion criteria and completed Visit 1, excluding participants with cardiac scintigraphy assessed as non-evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With HFpEF | Number of Participants According to TTR Genotypes Among Participants Diagnosed With ATTR-CM | TTR Genotype: Variant | 7 Participants |
| Participants With HFpEF | Number of Participants According to TTR Genotypes Among Participants Diagnosed With ATTR-CM | TTR Genotype: Wild-Type | 47 Participants |
| Participants With HFpEF | Number of Participants According to TTR Genotypes Among Participants Diagnosed With ATTR-CM | TTR Genotype: Not reported | 2 Participants |