Cardiac amyloidosis is a great masquerader that often results in misdiagnosis of this condition. Early clinical recognition is crucial for timely therapeutic interventions to improve survival in patients with cardiac amyloidosis. Currently, Food and Drug Administration (FDA)-approved medications work best if started early in the disease. Thus, to increase identification, disease awareness, expertise in diagnostic techniques, and a multidisciplinary team approach is essential. The majority of the patients (~90%) in the United States are treated in community hospitals, thus, it would be helpful for these hospitals to have their own designated, comprehensive cardiac amyloidosis center to provide care to the patients who are widespread in the community. Most of these patients are elderly, and it is difficult for these patients to travel long distances to academic amyloid centers. Our manuscript aims to provide a path to the development of cardiac amyloid centers at community hospitals.
1. Overview of Cardiac Amyloidosis
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy that commonly causes heart failure and results from the extracellular deposition of misfolded proteins, which configures the insoluble beta-pleated sheet structures called amyloid fibrils. Over 30 amyloid precursor proteins are identified, nine of which frequently cause CA, of which over 95% result from the amyloid light chain (AL) and amyloid transthyretin (ATTR) [1, 2, 3]. AL arises from misfolded monoclonal immunoglobulin light chains (produced from clonal plasma cells), and ATTR arises from misfolded transthyretin (TTR) protein (produced predominantly in the liver), resulting in AL-CA and ATTR-CA respectively. ATTR can occur either through mutation in transthyretin (variant-ATTR/ATTRv) or age-related processes without mutation in transthyretin (wild-type ATTR/ATTRwt). Thus, AL-CA, ATTRwt-CA, or ATTRv-CA are the most common types of CA [4]. Valine-to-isoleucine substitution at position 122 (Val122Ile) is the most common mutation causing ATTRv-CA in the USA, seen in 3.5% of African Americans, especially of Western African origin [5]. AL-CA is rare, with an annual incidence estimated to be 1 in 75,000 to 100,000 as of 2015, with cardiac involvement present in about 75% of patients [4]. The true prevalence of ATTR-CA in the population is unknown. However, several autopsy studies have shown the prevalence of ATTRwt amyloid deposits up to 20–25% in octogenarians and 37% in people over age 95 [2]. Cardiac involvement determines the prognosis in patients with amyloidosis, with median survival rates ranging from 3.6 to 4.8 years for ATTRwt-CA, 2.6 years for ATTRv-CA due to Val122Ile, and 5.8 years for ATTRv-CA due to other mutations and less than six months for AL-CA, if left untreated [4, 6]. Therefore, early clinical recognition is crucial for timely therapeutic interventions to improve survival in patients with CA.
2. Need for Cardiac Amyloidosis Centers
CA is a great masquerader because of its marked heterogeneity in terms of cardiac phenotype or systemic involvement, often resulting in misdiagnosis for other more common diseases such as hypertensive heart disease, aortic stenosis, or hypertrophic cardiomyopathy [7, 8]. As a result, many patients experience significant delays in receiving a correct diagnosis, with 31.8% of patients reporting consulting more than five physicians before receiving a correct diagnosis of amyloidosis [9]. To overcome these challenges, a multidisciplinary team approach involving expertise such as cardiologists, hematologists, neurologists, nephrologists, nuclear imaging experts, pathologists, genetic counselors, nurses, and specialty pharmacists is necessary. This approach involves identifying diagnostic clues or red flags for CA, screening high-risk patients with appropriate diagnostic tools and their appropriate interpretation, offering genetic testing and counseling, and providing treatment, including advanced therapies such as cardiac transplantation, thus highlighting the need for CA centers to provide all the facilities in one integrated setting.
The present era of CA is advancing significantly, allowing patients to survive for over a decade with treatment [4, 10]. Thus, patients with CA will require ongoing care from specialists to manage their chronic condition. However, not all patients have access to multidisciplinary care because of the limited availability of CA centers. For instance, as per the American Hospital Association’s annual survey for 2021, there are 6129 hospitals in the United States, of which 5157 are community hospitals [11]. As of April 2023, only 47 centers in the United States participated in the Transthyretin Amyloidosis Outcomes Survey (THAOS) registry, the largest global, multicenter, longitudinal observational survey [12]. This poses a challenge for patients who are spread out across this country to travel to these centers to seek medical care, as travel, in particular, is reported as the most significant challenge by nearly one-third of patients [13]. To make this care more accessible, more CA centers should be established in the community near where patients live. This will help reduce travel time, increase awareness among community physicians, prompt more referrals, and ultimately result in more CA screening and identification. To provide care to the growing patient population, there will also be a need for more specialists in CA, which CA centers can help provide by establishing fellowship programs allowing opportunities for physicians to train in CA. Moreover, as of 2022, only one FDA-approved disease-directed therapy, Tafamidis, is available for ATTR-CA; thus, more CA centers are needed to provide a platform for ongoing and future clinical trials in this field [4, 14].
Our objective is to provide a structured approach and steps to help establish a new comprehensive CA center in a community-based hospital setting.