Heart Failure: Don't Forget the Role of Amyloidosis

Heart Failure Clinical Trial

— TEAM-HF  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05501847
• Other study ID #: 20_RIPH2-23
• Status: Recruiting
• Phase: N/A
• Start date: July 27, 2023
• Est. completion date: June 2024

Study information

• Verified date: August 2023
• Source: University Hospital Center of Martinique
• Contact: Jocelyne CRASPAG, MSc
• Phone: 0596592698
• Email: jocelyne.craspag[@]chu-martinique.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 446
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyloidosis
• Heart Failure

Intervention

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.

Locations

Country	Name	City	State
Guadeloupe	Laurent LARIFLA	Pointe-à-Pitre
Martinique	CHU de Martinique	Fort-de-France

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Center of Martinique

Countries where clinical trial is conducted

Guadeloupe,  Martinique, 

References & Publications (4)

Arvanitis M, Chan GG, Jacobson DR, Berk JL, Connors LH, Ruberg FL. Prevalence of mutant ATTR cardiac amyloidosis in elderly African Americans with heart failure. Amyloid. 2017 Dec;24(4):253-255. doi: 10.1080/13506129.2017.1391086. Epub 2017 Oct 20. No abs — View Citation

Dungu JN, Papadopoulou SA, Wykes K, Mahmood I, Marshall J, Valencia O, Fontana M, Whelan CJ, Gillmore JD, Hawkins PN, Anderson LJ. Afro-Caribbean Heart Failure in the United Kingdom: Cause, Outcomes, and ATTR V122I Cardiac Amyloidosis. Circ Heart Fail. 20 — View Citation

Gabet A, Juilliere Y, Lamarche-Vadel A, Vernay M, Olie V. National trends in rate of patients hospitalized for heart failure and heart failure mortality in France, 2000-2012. Eur J Heart Fail. 2015 Jun;17(6):583-90. doi: 10.1002/ejhf.284. Epub 2015 May 6. — View Citation

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of cardiac amyloidosis in acute heart failure patients in the French West Indies	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	Patient demographic characteristics	Age, gender, ethnicity, locality	Baseline
Secondary	To compare the clinical characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure	New York Heart Association (NYHA) stage, Heart failure picture	Baseline
Secondary	To compare the biological (total bilirubin) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure	Biological assessment heart failure (total bilirubin) expressed in mg/L	Baseline
Secondary	To compare the biological (BNP or NT-proBNP) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure	Biological assessment heart failure (BNP or NT-proBNP) expressed in pg/mL	Baseline
Secondary	To compare the biological (thyroid stimulating hormone) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure	Biological assessment heart failure (thyroid stimulating hormone) expressed in mUI/l	Baseline
Secondary	To compare the biological (High-sensitivity (hs) cardiac troponin (cTn)) characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure	Biological assessment heart failure (High-sensitivity (hs) cardiac troponin (cTn)) expressed in µg/L	Baseline
Secondary	To compare the genotypic characteristics of heart failure patients with cardiac amyloidosis to other causes of heart failure	Presence of a mutation in the transthyretin gene	Baseline or through visit T2, an average of 6 months
Secondary	Describe the cases of amyloidosis identified according to the severity of cardiac involvement	Extra-cardiac impact (renal and liver function)	Baseline
Secondary	Describe the cases of amyloidosis according to the severity of the heart failure	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
Secondary	Ultrasound criteria predictive of amyloid with or no LVH =12 mm	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
Secondary	Diagnostic score for cardiac amyloidosis in acute heart failure	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

External Links

•   Frequency of cardiac amyloidosis inpatients with unexplained left ventricular hypertrophy: The Caribbean Amyloidosis Study