Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF (TTRinHFpEF)

Prevalence and Prediction of Transthyretin Amyloidosis in Ambulatory Patients With Heart Failure With Preserved Ejection Fraction

Recent studies have shown that transthyretin amyloidosis (ATTR) can sometimes cause a type of heart failure where the pumping function of the heart is normal, also known as Heart Failure with Preserved Ejection Fraction (HFpEF) or diastolic heart failure. In this single center diagnostic study, we will evaluate for ATTR in patients with HFpEF in order to to determine how frequently this occurs and how we can predict which heart failure patients may have TTR amyloidosis. Our goal is to identify amyloidosis in heart failure patients earlier so that they can start treatment.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Amyloidosis; Heart Failure, Diastolic; Transthyretin Amyloidosis
• Intervention / Treatment: Diagnostic test: 99mTc-pyrophosphate Scintigraphy

Detailed Description

Patients 65-years and older with HFpEF will be enrolled to participate in this single center, event driven (positive nuclear amyloid scan also known as 99mTc-pyrophosphate SPECT scan) study.

During the single study visit the following will be obtained:

• 99mTc-pyrophosphate SPECT scan
• Blood and DNA (optional) sample collection
• Questionnaires in regards to neuropathy, carpal tunnel, frailty, and Heart failure symptoms and how they may affect ones quality of life
• 6-Minute Walk Test
• ECG (electrocardiogram)
• Echocardiogram

Electronic health records will be reviewed for up to 5 years in order to determine hospitalization and survival of the study participants. Clinical outcomes of interest include a combined endpoint of days alive outside of the hospital from heart failure hospitalizations at one and five years, presence of autonomic neuropathy, presence of carpal tunnel syndrome, presence of polyneuropathy. Additionally, Individual clinical endpoints are also endpoints of interest.

The results from this study will be used to determine how frequently heart failure patients have transthyretin amyloidosis in their heart and better understand their symptoms. We hope that better understanding transthyretin amyloidosis in heart failure patients will help us identify affected patients so that they can receive treatment.

• Study Type: Interventional
• Enrollment (Estimated): 515
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jason Chen, BS; Phone Number: 617-643-1695; Email: jchen134@mgh.harvard.edu
• Study Contact Backup: Name: Laura Stockhausen, BS; Phone Number: 617-724-1339; Email: lstockhausen@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts general Hospital
      • Contact: NurAlima Grandison, BA
      • Principal Investigator: Hanna Gaggin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with a confirmed diagnosis of HFpEF.
• Age ≥65 years old

Exclusion Criteria:

• End stage chronic kidney disease on dialysis (CKD stage 5 as defined as eGFR <15mL/min)
• no history of HFrEF (LVEF<40%) with the exception of low LVEF in the setting of acute decompensation, AF RVR, ACS/MI, etc
• Negative 99mTc-pyrophosphate scan within a year
• Unable to lie down for 15 minutes for the 99mTc-pyrophosphate scan
• Known diagnosis of amyloidosis
• Severe valvular heart disease that is uncorrected (moderate to severe is considered exclusionary)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients 65 and older with Heart Failure with Preserved Ejection Fraction; Patients 65 years and older presenting to Massachusetts General Hospital with a known diagnosis of HFpEF and without a diagnosis of amyloidosis in the ambulatory (outpatient) setting will undergo a 99Tc-Pyrophosphate Scan to identify Cardiac Amyloidosis	Diagnostic test: 99mTc-pyrophosphate Scintigraphy; Cardiac Imaging Technique used to diagnose Transthyretin Cardiac Amyloidosis by use of 15 mCi of 99mTC-Pyrophosphate tracer; Other Names: PYP Scan; Pyrophosphate Scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnosis of 99mTc-pyrophosphate scan positive ATTR	A cardiac disease in which misfolded proteins aggregate into amyloid fibril and deposit interstitially, leading to diastolic dysfunction and heart failure	Day 1 (day of study visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New York Heart Association function classification	Classifies the severity of a patients Heart Failure in terms of their limitations during physical activity	Day 1 (day of study visit)
Impact of HF as assessed by Kansas City Cardiomyopathy Questionnaire	Kansas City Cardiomyopathy Questionnaire is a questionnaire that determines in the impact of Heart Failure on their health status, such as quality of life, symptoms, function, etc.)	Day 1 (day of study visit)
Exercise capacity as determined by a 6-minute walk test	The 6 minute walk test is used to determine an objective measurement of a patients aerobic capacity and endurance	Day 1 (day of study visit)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of autonomic neuropathy	Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events	Time from study Visit until the date of documented event up to 5 years after the study closure
Presence of carpal tunnel syndrome	Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events	Time from study Visit until the date of documented event up to 5 years after the study closure
Presence of polyneuropathy	Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events	Time from study Visit until the date of documented event up to 5 years after the study closure
Combined endpoint of days alive outside of hospital from HF hospitalizations at one and five years	Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events	Time from study Visit until the date of documented event up to 5 years after the study closure
Individual endpoints of all-cause mortality, cardiovascular mortality, all-cause hospitalizations, cardiovascular hospitalizations and HF hospitalizations.	Medical records and phone follow-up with patients and/or their physicians will allow the investigators to ascertain vital status and any significant clinical events	Time from study Visit until the date of documented event up to 5 years after the study closure

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Pfizer; Akcea Therapeutics; Alnylam Pharmaceuticals; Eidos Therapeutics, a BridgeBio company
• Investigators: Principal Investigator: Hanna K Gaggin, MD, Massachusetts general Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Amyloidosis; Heart Failure, Diastolic; Transthyretin Amyloidosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Proteostasis Deficiencies; Metabolism, Inborn Errors; Heredodegenerative Disorders, Nervous System; Amyloidosis, Familial; Amyloid Neuropathies; Heart Failure; Amyloidosis; Heart Failure, Diastolic; Amyloid Neuropathies, Familial; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Technetium Tc 99m Pyrophosphate
• Other Study ID Numbers: 2020P002061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No