Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis ...of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms.
These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central.
The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy.
A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Amyloidosis remains underdiagnosed, however newer diagnostic modalities and newer therapeutic agents have increased the awareness for this disease. The prevalence of cardiac amyloidosis in the ...Veterans Affairs population is unknown and there are now effective treatments for patients with amyloidosis and cardiomyopthy. The objective of this study is to describe the diagnosis of amyloidosis in the Veterans Affairs population.
We undertook a retrospective analysis of the Veterans Affairs Department of Veterans Affairs Informatics Computing Infrastructure database from 2000-2014. We queried the diagnosis of amyloidosis using the International Classification of Disease-9th revision -Clinical Modification Diagnosis (ICD) code of 277.3X. We calculated the incidence proportions as cases per 100,000 population per year.
A total of 5,639 patients with diagnosis codes for amyloidosis were identified during the study period, giving an incidence of 7.4 per 100,000 patients. Of them, 96% were men and 88% were older than 55 years old. The incidence increased over the years (Linear Trend Coefficient = 1.49, p-value = 0.001) and at a faster rate over the last years (Quadratic trend coefficient = 3.04, p-value < 0.001). The incidence increased predominately in patients from the Vietnam period, with a 2-fold increase from 2000 to 2014 (2.5 vs 5.1 per 100,000 patients, respectively).
Cases of amyloidosis continues to increase in the US Veterans population. Understanding the epidemiological trends and populations at risk will guide the development of tools to provide early diagnosis and appropriate access to care for patients with amyloidosis.
Cardiac amyloidosis (CA) can be difficult to diagnose, with a prolonged and often complex patient journey. The most common forms of CA include light-chain (AL) amyloidosis and transthyretin ...amyloidosis (hereditary or wild-type). The introduction of non-invasive diagnostic tools and emergence of novel therapies under investigation in clinical trials are boosting recognition of CA as a cause of heart failure (HF).
The diagnosis of CA is often delayed, and patients with the disease experience a heavy disease burden.
An online Harris Poll survey was conducted in the U.S. (Nov. 9-Dec. 10, 2018) among cardiologists who treat HF or CA and patients age ≥18 y and diagnosed with these diseases. Participants included 505 cardiologists who reported treating ≥1 patient/mo with HF or CA and 335 patients (HF not due to CA, n=260; CA, n=75).
Cardiologists (mean age, 51.3 y; male, 87%; city/suburban practice, 87%; mean clinical experience, 20.2 y) saw an average of 433 patients with HF and 14.5 patients with CA in the last year. Cardiologists estimated that 41%, 28%, and 31% of their patients with CA had AL, hereditary, and wild-type disease, respectively. Nearly half of cardiologists (45%) noted an increased number of patients with CA managed in their practice compared to 5 years ago. Nearly all cardiologists (>99%) believed patients with CA experience delays in diagnosis; the most common reasons were misdiagnosis and low awareness of CA and diagnostic tests (Fig. A). Most cardiologists (96%) requested additional education on CA (Fig. B). Patients with CA were younger than those with HF (mean age, 45.6 vs 58.7 y; p<0.0001) and more likely to be men (73% vs 48%; p<0.001). Patients with CA saw more healthcare providers (HCPs) than those with HF to address their symptoms before diagnosis (mean, 5 vs. 2; p<0.01) and had longer travel times to see their HCP after diagnosis (mean, 3.4 vs 1.2 h; p<0.0001). Similar proportions of patients with HF or CA put their lives on pause due to their disease (68% and 76%, respectively), but a higher proportion of patients with CA reported a heavy disease burden on several aspects of daily living (Fig. C).
Despite recent advances, delayed diagnosis of CA remains a challenge to cardiologists and the disease continues to disrupt patients’ lives. Additional research on the characteristics of the disease and educational campaigns are needed to enhance recognition of CA and shorten the patient diagnostic journey.
Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is a progressive, life-threatening condition that is underdiagnosed and frequently recognized at a late stage. ATTR-CM poses unique diagnostic and ...therapeutic challenges that often require referral to an Amyloidosis Program (AP). APs have developed strategic practices to provide multidisciplinary comprehensive care, and their best practices have not yet been studied as a group.
Gaining insight on AP best practices may help provide guidance to health care providers who see patients with heart failure about early ATTR-CM diagnosis, comprehensive patient care, improved disease management, and apt timing/consideration of referral to an AP.
A qualitative survey was conducted by telephone or e-mail from Oct 14, 2019 to Feb 3, 2020. Interviewees were 15 cardiologists and 9 nurses with ATTR-CM expertise from 15 US APs; 16 patients with ATTR-CM (mean age, 69 y; range, 45-81 y) treated in APs; and 4 patient advocates from amyloidosis support groups.
The majority of APs included in the survey have been in existence for ≥5 years. Best practices most often cited by cardiologists were diagnostic capability and staff expertise (Figure). The greatest priorities for establishing an AP were building a multidisciplinary approach, ensuring expertise and quality of diagnostic techniques, and allocating time for patient education. Most APs have group meetings to discuss cases, and many include genetic counselors and specialty pharmacists plus a range of clinician/nurse specialists on their teams. Most patients were referred to APs by their physicians, and many travel ≥3 hours to visit APs. Patients described the ‘ideal’ AP as one that provides physicians with expertise in ATTR-CM, sufficient time with patients, comprehensive patient care, and opportunities to participate in research/clinical trials (Figure). The majority of APs host patient support group meetings, and patient advocacy groups provide support for APs with physician/patient education and research.
APs offer comprehensive care based on staff expertise in ATTR-CM, a multidisciplinary approach, advanced diagnostics, and time dedicated to patient education. Raising awareness of AP best practices among healthcare providers can reinforce the benefits of early referral and comprehensive care for patients with ATTR-CM.
Aim: The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including ...transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. Objective: To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. Method: A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Results: Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. Conclusion: The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.
Plain language summary What is this study about? This study looked at people with cardiomyopathy, a disease in which the heart loses its ability to pump blood effectively around the body. Some cases of cardiomyopathy are caused by problems with a protein called transthyretin. In clinical trials for cardiomyopathy, doctors often use the number of hospitalizations or deaths to assess a drug's effectiveness. However, this may not tell the whole story. The six-minute walk test (6MWT) is another way of assessing the severity of cardiomyopathy. It measures how far a person can walk on flat ground in 6 min, which can be important to people with heart conditions as it affects whether they can perform normal daily activities. Using the 6MWT in clinical trials may make it easier to assess new drugs and give a more holistic view of a drug's effects. Our study explored the link between the 6MWT and the risk of death or hospitalization in people with cardiomyopathy. What were the results? We analyzed 41 studies that measured 6MWT and rates of hospitalization and/or death in people with cardiomyopathy. The results showed that those who could walk further during the 6MWT were less likely to die or be hospitalized than those who could walk a shorter distance. Similar findings were seen in people with cardiomyopathy caused by transthyretin. What do the results mean? Our results suggest that the 6MWT is a valid and meaningful measure of the severity of cardiomyopathy, supporting its use as a key assessment in cardiomyopathy clinical trials.
Background: Gastrointestinal bleeding (GIB) is a leading cause of morbidity during continuous-flow left ventricular assist device (CF-LVAD) support. GIB risk assessment could have important ...implications for candidate selection, informed consent, and postimplant therapeutic strategies. The aim of the study is to derive and validate a predictive model of GIB in CF-LVAD patients. Methods and Results: CF-LVAD recipients at the Utah Transplantation Affiliated Hospitals program between 2004 and 2017 were included. GIB associated with a decrease in hemoglobin ≥2 g/dL was the primary end point. A weighted score comprising preimplant variables independently associated with GIB was derived and internally validated. A total of 351 patients (median age, 59 years; 82% male) were included. After a median of 196 days, GIB occurred in 120 (34%) patients. Independent predictors of GIB included age >54 years, history of previous bleeding, coronary artery disease, chronic kidney disease, severe right ventricular dysfunction, mean pulmonary artery pressure <18 mm Hg, and fasting glucose >107 mg/dL. A weighted score termed Utah bleeding risk score, effectively stratified patients based on their probability of GIB: low (0–1 points) 4.8%, intermediate (2–4) 39.8%, and high risk (5–9) 83.8%. Discrimination was good in the development sample (c-index: 0.83) and after internal bootstrap validation (c-index: 0.74). Conclusions: The novel Utah bleeding risk score is a simple tool that can provide personalized GIB risk estimates in CF-LVAD patients. This scoring system may assist clinicians and investigators in designing tailored risk-based strategies aimed at reducing the burden posed by GIB in the individual CF-LVAD patient and healthcare systems.
The new United Network for Organ Sharing (UNOS) donor heart allocation system gives priority to patients supported with nondischargeable mechanical circulatory support (MCS) devices while awaiting ...heart transplant. Whether there has been a change in temporary MCS use in cardiac intensive care units (CICUs) since the implementation of this policy is unknown.
To examine whether the UNOS donor heart allocation system revision in October 2018 was associated with changes in temporary MCS use in CICUs and whether temporary MCS use differed between US transplant centers and US nontransplant centers and Canadian centers.
In this cohort study, 14 centers from the Critical Care Cardiology Trials Network (CCCTN), a multicenter network of tertiary CICUs in North America, contributed 2-month snapshots of consecutive medical CICU admissions between September 1, 2017, and September 1, 2018 (prerevision period), and October 1, 2018, and September 1, 2019 (postrevision period). CICUs were classified as US transplant centers (n = 7) or other CICUs (US nontransplant centers or Canadian centers; n = 7).
Revision to the UNOS donor heart allocation system.
Treatment with temporary MCS (intra-aortic balloon pump, microaxial intracardiac ventricular assist device, percutaneous centrifugal ventricular assist device, venoarterial extracorporeal membrane oxygenation, or surgically implanted, nondischargeable MCS device) during hospital admission.
A total of 384 admissions for acute, decompensated, heart failure-related cardiogenic shock (ADHF-CS) were included, among which 248 (64.6%) were to US transplant centers; 126 admissions (51%) were in the prerevision period and 122 (49%) were in the postrevision period. The mean (SD) patient age was 61.2 (14.6) years; 246 patients (64.1%) were male. The proportion of admissions with ADHF-CS managed with temporary MCS at US transplant centers significantly increased from 25.4% (32 of 126 admissions) before to 42.6% (52 of 122 admissions) after the UNOS allocation system changes (P = .004). In other CICUs, the proportion did not significantly change (24.5% 13 of 53 admissions to 24.1% 20 of 83 admissions; P = .95). After multivariable adjustment, patients admitted to US transplant centers in the postrevision period were more likely to receive temporary MCS compared with those admitted in the prerevision period (adjusted odds ratio, 2.19; 95% CI, 1.13-4.24; P = .02).
In the year after implementation of the new UNOS donor heart allocation system, temporary MCS use in patients admitted with ADHF-CS increased in US transplant centers but not in other CICUs. Whether this shift in practice will affect outcomes of patients with ADHF-CS or organ distribution should be evaluated.
Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific ...etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units.
The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions.
Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%-50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%-100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use.
There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.
•A majority (67%) of patients with cardiogenic shock (CS) admitted to North American cardiac intensive care units have heart failure-related CS (HF-CS) unrelated to acute myocardial ...infarction.•Approximately 1 in 4 patients with HF-CS present with de novo HF-CS, defined as no known prior history of heart failure.•Compared to patients with acute-on-chronic HF-CS, those with de novo HF-CS have more severe shock, greater end-organ injury and higher in-hospital mortality.
Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown.
We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017–2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th–75th: 5–11) vs acute-on-chronic HF-CS (6; 25th–75th: 4–9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05–1.75, P = 0.02).
Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.
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