Heart Failure: Don't Forget the Role of Amyloidosis (TEAM-HF)

August 25, 2023 updated by: University Hospital Center of Martinique

Prevalence of Cardiac Amyloidosis in Patients With Hospitalization for Acute Heart Failure in the French West Indies

Heart failure is defined as the inability of the heart to provide sufficient output to meet the needs of the body.

It can occur in the course of a myocardial infarction, angina pectoris, hypertension, etc. Its frequency increases with age.

It is a major public health problem.

Heart failure first appears during exercise, then at rest. Initially, the heart tries to adapt to the loss of its contraction force by accelerating its beats (increase in heart rate), then it increases in volume (thickening of the walls or dilation of the cardiac cavities). This extra workload for the heart eventually leads to heart failure.

Cardiac amyloidosis is a possible cause of the disease in the West Indian population.

Cardiac amyloidosis is a rare disease related to our own proteins that will accumulate and cluster together to form abnormal protein deposits that will eventually lead to heart failure.

Cardiac amyloidosis particularly affects West Indians, due to the high frequency in this population of a genetic anomaly associated with the disease: the Valine 122 Isoleucine (Val122l) mutation of the transthyretin gene (protein transthyretin in which isoleucine is substituted for valine at position 122 (Ile 122)).

Early detection of amyloidosis appears essential for the implementation of appropriate therapies and therefore for an improvement in patient survival.

For this it seems important to better specify the frequency of cardiac amyloidosis in heart failure in the French West Indies.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The heart supplies the organs with oxygen and nutrient-rich blood. During exercise, the heart adapts by increasing the rate of contraction and the rate of blood flow.

Heart failure occurs when the heart loses its muscular strength and its normal capacity to contract; it no longer pumps enough blood to allow the organs to receive enough oxygen and nutrients, which are essential for their proper functioning.

This syndrome is frequent and serious with a prevalence of 2 to 3% in Europe and a high morbidity and mortality (1st cause of hospitalization with more than 150,000 hospitalizations per year in France, a mortality of 50% at 5 years, i.e. more than most cancers). This mortality is even higher in the West Indies, with an excess of premature mortality related to heart failure of +32.9% in Martinique and +86.9% in Guadeloupe compared with metropolitan France (average annual mortality rate for heart failure in 2008-2010 per 100,000 in habitants under 65 years of age).

Some studies have indeed shown a higher prevalence of heart failure in the Afro-Caribbean and Afro-American population with etiologies that differ from the Caucasian population. Among them, transthyretin (TTR) amyloidosis is rare in Europe but very common in African descendants with a prevalence of 3.4% of a transthyretin gene mutation (V122l) in this population (likely to induce hereditary amyloidosis after the fifth decade). It is a serious disease with a median survival of 2 to 6 years depending on the study and is often under-diagnosed with late detection at the time of a major cardiovascular event, such as a stroke or acute heart failure. Screening is done by imaging (cardiac MRI or bone scintigraphy with labelled diphosphonates). According to a study carried out in the Cardiology Department of the Martinique University Hospital (TEAM Amyloidosis study), one out of three left ventricular hypertrophy (LVH) (parietal thickness ≥ 15 mm), diagnosed by echocardiography, is amyloidosis. A study published by Thibaud Damy's team in 2015 already found a 5% prevalence of TTR gene mutation in patients with LVH. It is now accepted that systematic screening for amyloidosis is necessary in cases of LVH > 12 mm associated with at least one risk factor for amyloidosis ("red flags") in order to implement appropriate therapies and thus improve patient survival.

The study by Dungu et al. reports that cardiac amyloidosis is an underestimated etiology of acute heart failure in Afro-Caribbean immigrants in London. The study found a high prevalence of cardiac amyloidosis at 11.4% among 211 African-Caribbean immigrants compared to a Caucasian population (1.6%), with a higher mortality of these patients compared to patients with another cause of heart failure (median survival 2.3 years versus 7 years for other etiologies). The study by Arvanitis et al. describes a 5.1% prevalence of the transthyretin gene mutation (V122l) in 101 African Americans with heart failure (compared to 8.5% of mutation carriers among African-Caribbean immigrants in the Dungu study).

In these two studies, the prevalences of amyloidosis and the V122I mutation are probably underestimated, given the absence of systematic screening of all heart failure cases and the fact that only patients with left ventricular hypertrophy on transthoracic echography were targeted.

In addition, amyloidosis can take different forms from those usually described. Occasional observations in our experience at the University Hospital of Martinique have found cases of heart failure with dilated cardiomyopathy (DCM), associated with transthyretin cardiac amyloidosis. Several similar observations have been found in the literature.

The study hypothesise is that cardiac amyloidosis is as common, or more common, in acute heart failure in the French West Indies than elsewhere. A systematic screening for amyloidosis in all patients with acute heart failure would allow early initiation of appropriate treatment and improve their long-term outcome.

Study Type

Interventional

Enrollment (Estimated)

446

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Guadeloupe
      • Pointe-à-Pitre, Guadeloupe, 97110
        • Not yet recruiting
        • Laurent LARIFLA
        • Contact:
        • Principal Investigator:
          • Laurent LARIFLA, MD, Sc.D
  • Martinique
      • Fort-de-France, Martinique, 97261
        • Recruiting
        • CHU de Martinique
        • Sub-Investigator:
          • Jocelyn INAMO, MD, PhD
        • Contact:
        • Principal Investigator:
          • Astrid MONFORT BRAFINE, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

46 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Present functional or physical signs of acute heart failure (exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fatigue, jugular turgor, hepato-jugular reflux, edema of the lower limbs, galloping noise, crackles on pulmonary auscultation)
  • BNP >100pg/mL or NT-proBNP >300pg/mL
  • Diagnosis of heart failure confirmed by the cardiologist
  • Be affiliated to a social security plan or beneficiary
  • Be able to receive and understand information related to the research
  • Able to freely express his/her non-opposition or informed and written consent.

Exclusion Criteria:

  • Person under legal protection (guardianship, curatorship, safeguard of justice), and person deprived of liberty.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Patient with ventricular hypertrophy
Screening for cardiac amyloidosis in a patient with heart failure and ventricular hypertrophy is performed as part of routine care according to a standardised care protocol that follows the Gullimor algorithm.
Experimental: Patient with no ventricular hypertrophy

In the context of TEAM-HF research, the heart failure patient without ventricular hypertrophy will undergo a bone scan.

If the diagnosis of amyloidosis is most often suspected on the electrocardiogram and cardiac echography, only cardiac MRI or bone scan with diphosphonates (for transthyretin amyloidosis) can make the diagnosis.
Radiation: Patient with no ventricular hypertrophy

Patients without LVH ≥ 12 mm will routinely receive a bone scan as part of the study.

In case of cardiac fixation on bone scan, the patient will be managed as part of routine care according to a standardized care protocol that follows Guillmor's algorithm: monoclonal abnormality testing on biological blood samples +/- genotyping, in order to specify the senile or mutated character of TTR cardiac amyloidosis and to give the genotype.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence of cardiac amyloidosis in acute heart failure patients in the French West Indies
Time Frame: 18 months +/- 8 days post inclusion

The prevalence of cardiac amyloidosis in acute heart failure patients in Martinique and Guadeloupe over the study period will be determined by the following ratio

Number of cardiac amyloidosis (old + new cases) in acute heart failure patients with hospital referral over the study period divided by the total number of acute heart failure patients with hospital referral over the period concerned

This prevalence will be expressed per 10,000 and 100,000 people.
18 months +/- 8 days post inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient demographic characteristics
Time Frame: Baseline
Age, gender, ethnicity, locality
Baseline
To compare the clinical characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure
Time Frame: Baseline
New York Heart Association (NYHA) stage, Heart failure picture
Baseline
To compare the biological (total bilirubin) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure
Time Frame: Baseline
Biological assessment heart failure (total bilirubin) expressed in mg/L
Baseline
To compare the biological (BNP or NT-proBNP) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure
Time Frame: Baseline
Biological assessment heart failure (BNP or NT-proBNP) expressed in pg/mL
Baseline
To compare the biological (thyroid stimulating hormone) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure
Time Frame: Baseline
Biological assessment heart failure (thyroid stimulating hormone) expressed in mUI/l
Baseline
To compare the biological (High-sensitivity (hs) cardiac troponin (cTn)) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure
Time Frame: Baseline
Biological assessment heart failure (High-sensitivity (hs) cardiac troponin (cTn)) expressed in µg/L
Baseline
To compare the genotypic characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure
Time Frame: Baseline or through visit T2, an average of 6 months
Presence of a mutation in the transthyretin gene
Baseline or through visit T2, an average of 6 months
Describe the cases of amyloidosis identified according to the severity of cardiac involvement
Time Frame: Baseline
Extra-cardiac impact (renal and liver function)
Baseline
Describe the cases of amyloidosis according to the severity of the heart failure
Time Frame: Baseline
Biomarkers (brain natriuretic peptide (BNP) or N-terminal fragment of probrain natriuretic peptide (NT-proBNP), High-sensitivity (hs) cardiac troponin (cTn)), etc expressed in sub-units of grams / sub-units of liters
Baseline
Ultrasound criteria predictive of amyloid with or no LVH ≥12 mm
Time Frame: Baseline or up to 24 weeks post inclusion
Ultrasound criteria predictive of amyloid involvement according to the presence or absence of LVH ≥12 mm by detailed analysis of cardiac echography
Baseline or up to 24 weeks post inclusion
Diagnostic score for cardiac amyloidosis in acute heart failure
Time Frame: Through study completion, an average of 1 year

This score will be composed of clinical, biological and imaging characteristics significantly associated with the presence of cardiac amyloidosis in a heart failure patient following the implementation of multivariate logistic regression modelling. The internal validation of this score will be determined by assessing :

  • The discrimination parameters of the score: sensitivity, specificity, and area under the Receiver Operating Characteristic (RO)C curve
  • Calibration of the score: comparison of predicted and observed risks (Hosmer-Lemeshow test).
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Center of Martinique

Investigators

  • Study Director: Astrid MONFORT BRAFINE, MD, CHU de Martinique

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 27, 2023

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

August 8, 2022

First Submitted That Met QC Criteria

August 11, 2022

First Posted (Actual)

August 16, 2022

Study Record Updates

Last Update Posted (Actual)

August 28, 2023

Last Update Submitted That Met QC Criteria

August 25, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20_RIPH2-23

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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