Transthyretin Cardiac Amyloidosis in HFpEF

Prevalence of Transthyretin Cardiac Amyloidosis in Heart Failure With Preserved Ejection Fraction: A Community Study

To estimate the prevalence of transthyretin cardiac amyloidosis (TTR-CA) among Heart Failure with Preserved Ejection Fraction (HFpEF) patients with increased LV wall thickness in Southeast Minnesota using 99mTc-PYP single-photon positive emission computed tomography with computed tomography (SPECT/CT).

Study Overview

• Status: Completed
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: 99mTc-PYP

Detailed Description

Residents of Southeast Minnesota over 60 years of age with an inpatient or outpatient diagnosis of heart failure (HF) will be consecutively identified in real-time using a natural language processing (NLP) search engine, their HF diagnosis validated, and those with a recent (≤ 12 months) echocardiogram documenting a preserved EF( ≥ 40%) and LV wall thickening will be consented to undergo venipuncture, urine collection and 99mTc-PYP SPECT/CT imaging to rule in/out the diagnosis of TTR-CA. Hence, the prevalence of TTR-CA will be defined. To place this prevalence in perspective of the global HFpEF cohort in the community, a rigorous screening log will be maintained to allow generation of a comprehensive CONSORT diagram. Importantly, baseline characteristics of patients who qualify for our study but decline to consent will still be collected provided that consent for use of their records for medical research had previously been granted.

• Study Type: Interventional
• Enrollment (Actual): 287
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Resident of Southeastern Minnesota (Olmsted, Dodge, Fillmore, Mower, Freeborn, Wabasha, or Steele County)
2. Current diagnosis of HF per NLP search
3. Age > 60 years

4. Clinically obtained echocardiogram within 12 months of index visit showing:

   1. EF ≥ 40% and
   2. Increased Left Ventricular (LV) wall thickness as defined by an end-diastolic left ventricular septal or posterior wall thickness (LVWTd) ≥ 20% above the upper limit of normal measured by 2D or M-mode imaging in the parasternal long (2D) or short (M-mode) axis view (≥12 mm).

5. Objective evidence of HF defined as one or more of the following present within 24 months of index visit:

   1. Meet Framingham Criteria at index visit (In-patient or outpatient)
   2. Previous HF hospitalization
   3. Invasive hemodynamic documentation of elevated pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) (> 18 mmHg at rest or > 25 mmHg with exercise)
   4. Left atrial enlargement + loop diuretic for HF(clinically obtained) N-terminal pro b-type natriuretic peptide (NT-proBNP) > 300 (sinus rhythm) or >900 (atrial fibrillation) pg/mL

Exclusion Criteria

1. Documentation of previous EF < 40%
2. Any cardiac surgery or major chest trauma within 4 weeks of index visit

3. Presence or history of hemodynamically significant left sided valvular disease defined as:

   1. Greater than mild mitral stenosis
   2. Intrinsic mitral valve disease (prolapse, flail) with greater than moderate regurgitation
4. Myocardial infarction within 4 weeks of index visit defined by typical angina, EKG changes and significant change in serial troponins. Note that chronic troponin elevation is extremely common in cardiac amyloidosis. Hospitalized patients with troponin elevation but no significant change (delta) on serial testing will NOT be excluded.
5. Prior or current exposure to Plaquenil (Hydroxychloroquine)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: SPECT/CT; 99mTc-PYP single-photon positive emission computed tomography with computed tomography	Drug: 99mTc-PYP; Radioisotope used in the SPECT/CT imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of TTR-CA	Determine the prevalence of Transthyretin Cardiac Amyloidosis in a community based cohort of consecutive Heart Failure with Preserved Ejection Fraction patients with increased Left Ventricular wall thickness using 99mTc-Pyrophosphate (99mTc-PYP) single-photon positive emission computed tomography with computed tomography (SPECT/CT).	Baseline

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Pfizer
• Investigators: Principal Investigator: Omar F Abou Ezzeddine, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2017
• Primary Completion (ACTUAL): March 31, 2020
• Study Completion (ACTUAL): March 31, 2020

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: January 23, 2018
• First Posted (ACTUAL): January 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 19, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Heart Failure; Amyloidosis; Diastolic Heart Failure; Heart Failure with Preserved Ejection Fraction; Transthyretin Cardiac Amyloidosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Proteostasis Deficiencies; Heart Failure; Amyloidosis
• Other Study ID Numbers: 17-003021

Drug and device information, study documents

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