**3. Epidemiology**

About >95% of cases of cardiac amyloidosis are caused or related to light chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis.

### **3.1 AL-amyloidosis**

AL amyloidosis has an incidence of approximately 4000 new cases of amyloidosis annually in the United States. However, the actual incidence may be higher due to the disease under diagnosis. While the incidence is thought to be equal in males and females, about 60% of patients referred to amyloid centers are males [15]. However, only half of these patients present cardiac manifestations of systemic (AL) amyloidosis. Once heart failure symptoms ensue, prognosis is poor with a median survival of <6 months if plasma cell dyscrasia is left untreated [16]. In AL-cardiac amyloidosis, poor prognosis is associated with increased LV relative wall thickness, older age, NYHA class, elevated pro-BNP, and increased C-reactive proteins [16, 17].

#### **3.2 ATTR amyloidosis**

On the other hand, ATTR amyloidosis, which was thought to be a rare cause for CA, has recently been more frequently diagnosed. This is a result of the use of new cardiac imaging techniques and increased availability of imaging and diagnostic tools clinical practices, that have revolutionized the diagnosis of cardiac diseases. However, despite advances and availability in imaging techniques, this condition is still frequently underdiagnosed due its myriad of signs and symptoms, which are often associated with other diseases, leading to a poorly delineated prevalence of the disease. Earlier reports of patients undergoing noninvasive diagnosis with patients older than 60 years, Gonzalez et al. found a staggering 13% prevalence of CA in patients admitted with clinical diagnosis of decompensated heart failure with preserved ejection fraction [13]. Meanwhile, AbouEzzeddine et al. performed a community based-setting cohort study in which ATTR-CM was found in a substantial number of older male patients with heart failure with preserved ejection fraction (HFpEF) (2.5% with 95% CI, 1.4–4.0%). This study highlights the importance of systemic screening for CA in male patients with HFpEF and LV wall thickening [14].

#### *3.2.1 ATTRwt*

ATTRwt almost exclusively occurs in male patients 70 years or older with a median survival after the onset of heart failure of 7.5 years [18]. The average

#### *Cardiac Amyloidosis DOI: http://dx.doi.org/10.5772/intechopen.109522*

worldwide prevalence is estimated to be 1/6000 [19]. Interestingly autopsy studies on from patients with antemortem diagnosis of HFpEF demonstrated presence of fibrillar deposits within the heart in 25% of the patients older than 80 years of age [20]. Moreover several studies have shown that one in seven elderly patient with aortic stenosis also suffer from cardiac amyloidosis [5]. While the exact mechanism or reason behind the frequent coexistence of both diseases in such patients is not fully understood, several hypotheses have been drawn in aims to provide a plausible explanation. The coexistence of severe aortic stenosis with ATTRwt has been shown to not have a significant impact in patient survival; special considerations should be taken with these patients at the time of treatment and will be addressed in greater detail later in the chapter. In comparison to ATTRv, ATTRwt almost exclusively affects the heart with involvement of both atrial and ventricular chambers and frequent incidence of conduction disorder and arrhythmias [20]. However, patients with ATTRwt have been shown to have some extracardiac manifestations of the disease such as musculoskeletal involvement like carpal tunnel syndrome in up to 33–49%, traumatic bicep rupture 33%, and lumbar stenosis 37% [21–23]. Extracardiac symptoms can precede cardiac ones up 5–7 years before cardiac amyloidosis diagnosis [24].

#### *3.2.2 ATTRv*

ATTRv onset has been shown to occur earlier in males than in females. Interestingly, the age of onset is progressively earlier in successive generations [11]. From the hereditary subtypes, the mutations known to have cardiac effects are TTR V30M, t TTR V122I, and TTR T60A. Most of these mutations are found clustered into distinct ethnicity groups and/or within certain geographical areas. Its inheritance has an autosomal dominant pattern [25]. The V30M mutation is the most common mutation worldwide, especially in parts of Portugal, Japan, and northern Sweden. Nevertheless, it has also been identified in Spain, France, South America, and some nonendemic areas of Africa. It has a slight female predominance with a bimodal presentation with earlier onset of V30M ATTR symptoms being mostly neurological and late-onset symptoms that present with both cardiomyopathic and polyneuropathic involvement [26].

On the other hand, the most common mutation in the US associated with lateonset cardiomyopathy is V122I. It is frequently diagnosed among African Americans with an incidence of 3–4% compared to 0.44% among white individuals. Moreover, within African American population this mutation can be found in up to 10% of the patients over 65 years of age who have developed severe HF [27]. The T60A variant is the second-most-common TTR variant in the US and the most common in the UK and Ireland, affecting approximately 1% of the population of north-western Ireland. It has an unknown gender distribution which occurs in patients >60 years of age with cardiac involvement as well as autonomic and peripheral neuropathies [10, 11, 27]. However, even though there are no set gender distribution male patients tend to have a mean age of presentation of 60–65 years of age, while female patients tend to have a latter onset. ATTRv is an important cause of heart failure that disproportionately affects people of African descent. Despite the high burden of ATTRv among black individuals, just a few studies include African American patients and most of the clinical data, we have for ATTRv come from North America and Europe. Moreover, despite the known and well-established predisposition to cardiovascular diseases within other minority groups such as Hispanic/Latino population, the only minority

group to be included and studied in clinical trials so far has been African American patients [28]. There is no known clinical data to describe epidemiological characteristics of ATTRv in the Hispanic/Latino population. Nevertheless, efforts to promote earlier identification of ATTRv in general practice will improve clinical outcomes for all groups.
