heart failure: don't forget the role of amyloidosis

Conditions: Heart Failure

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.

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.

Eligibility criteria:
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.

Keywords: ventricular hypertrophy amyloidosis cardiac transthyretin gene mutation