Prognosis Of Cardiac Amyloidosis Research Articles

Cardio-Hepatic Interaction in Cardiac Amyloidosis.

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.

Cardiac Amyloidosis: Mutimodality Imaging for Diagnosis and Prognosis

Abstract Cardiac amyloid cardiomyopathy (CM) is a rapidly progressive disease that is frequently underrecognized and frequently diagnosed late in a significant number of individuals suffering from heart failure. Cardiac amyloid infiltration resulting in myocardial hypertrophy and restrictive CM is primarily caused by the misfolding of precursor proteins such as transthyretin, light chain immunoglobulin, and apolipoprotein AI-IV. The utilization of echocardiography, cardiac magnetic resonance, and bone avid radiotracer scintigraphy are essential in establishing a reliable diagnosis and prognosis of cardiac amyloidosis in the majority of patients. However, in certain clinical scenarios, the use of cardiac or extracardiac biopsy is necessary. There are significant developments in the understanding of the pathobiology of amyloid formation, which has paved the way for the development of new-targeted therapies, specifically for transthyretin cardiac amyloidosis. Imaging techniques are developing to monitor quantitatively the progression and regression of cardiac and systemic amyloid infiltration.

Amylo-AFFECT-QOL, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis

Amylo-AFFECT-QOL, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis

Value of nuclide scintigraphy in the diagnosis and prognosis of cardiac amyloidosis.

Amyloidosis is a local or systemic disease caused by the deposition of misfolded proteins outside the cell, with rapid progression, and dire prognosis. Common types of cardiac amyloidosis are monoclonal immunoglobulin light chain amyloidosis (AL-CA) and transthyretin cardiac amyloidosis (ATTR-CA). Nuclear medicine examinations can be accurate, rapid, and non-invasive to help diagnose diseases and can effectively predict the prognosis of patients with CA. Technetium (99Tcm)-labeled bisphosphonate imaging has been included in the consensus of experts and has become the first-line imaging method for the diagnosis of ATTR-CA. 123I-metaiodoenzylguanidine (MIBG) as a norepinephrine analogue can effectively assess cardiac sympathetic innervation in patients with CA. Aβ- amyloid imaging agents such as 11C-pittsburgh compound B and 18F-flubetaben are expected to be new techniques for diagnosing AL-CA and incorporating them into cardiac staging systems for AL-CA patients in the future. New imaging agents such as 18F-NaF has been widely used in the diagnosis, treatment response monitoring, and prognosis assessment of CA. Summarizing the research value of nuclide imaging in CA may provide new ideas for clinical realization of early detection of CA and accurate assessment of disease prognosis.

Status and Future Directions of Therapeutics and Prognosis of Cardiac Amyloidosis.

Accumulation of aberrant proteins in the heart causes cardiac amyloidosis, an uncommon and complicated illness. It can be classified into two main types: light chain (AL) and transthyretin (ATTR). The diagnosis of cardiac amyloidosis is challenging due to its non-specific clinical presentation and lack of definitive diagnostic tests. Diagnostic accuracy has increased with the advent of modern imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Depending on the severity of cardiac amyloidosis, a number of treatments may be attempted and specified according to the subtype of amyloidosis and the presence of complications. However, there are still significant challenges in treating this condition due to its complexity and lack of effective treatments. The prognosis for patients with cardiac amyloidosis is poor. Despite recent advances in diagnosis and treatment, there is still a need for more effective treatments to improve outcomes for patients with this condition. Therefore, we aim to review the current and future therapeutics reported in the literature and among ongoing clinical trials recruiting patients with CA.

Prognosis in cardiac amyloidosis: Data from three-dimensional speckle-tracking echocardiography.

The authors declare no potential conflict of interest.

Amylo-AFFECT-QOL, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis.

Self-reported questionnaires are useful for estimating the health-related quality of life (HR-QoL), impact of interventions, and prognosis. To our knowledge, no HR-QoL questionnaire has been developed for cardiac amyloidosis (CA). This study aimed to validate Amylo-AFFECT-QOL questionnaire to assess HR-QoL and its prognostic value in CA. A self-reported questionnaire, "Amylo-AFFECT" had been designed and validated for CA symptoms evaluation and screening by physicians. It was adapted here to assess HR-QoL (Amylo-AFFECT-QOL) and its prognostic value in CA. To validate the theoretical model, internal consistency and convergent validity were assessed, particularly correlations between Amylo-AFFECT-QOL and the HR-QoL Minnesota Living Heart Failure (MLHF) questionnaire. Amylo-AFFECT-QOL was completed by 515 patients, 425 of whom (82.5%) had CA. Wild-type and hereditary transthyretin amyloidosis (ATTRwt and ATTRv) and immunoglobulin light-chain amyloidosis (AL) were diagnosed in 47.8, 14.7, and 18.8% of cases, respectively. The best HR-QoL evaluation was obtained with five dimensions: "Heart failure," "Vascular dysautonomia," "Neuropathy," "Ear, gastrointestinal, and urinary dysautonomia," and "Skin or mucosal involvement." The global Amylo-AFFECT-QOL and MLHF scores showed significant positive correlations (rs = 0.72, p < 0.05). Patients with a final diagnosis of CA had a global Amylo-AFFECT-QOL score significantly higher than the control group composed by patients with other diagnoses (22.2 ± 13.6 vs. 16.2 ± 13.8, respectively, p-value < 0.01). According to the Amylo-AFFECT-QOL global results, ATTRv patients' QoL was more affected than AL patients' QoL or ATTRwt patients' QoL. Patients with a higher HR-QoL score had a greater risk of death or heart transplant after 1 year of follow-up (log-rank < 0.01). Amylo-AFFECT-QOL demonstrates good psychometric properties and is useful for quantifying HR-QoL and estimating CA prognosis. Its use may help to improve overall management of patients with CA.

Hemodynamic Profiling and Prognosis in Cardiac Amyloidosis.

Little information is available on the prognostic relevance of cardiac hemodynamic cutoffs in cardiac amyloidosis (CA) and its subtypes. Consecutive patients diagnose with light chain-CA or transthyretin CA undergoing right heart catheterization were analyzed. Prognostic relevance of classic hemodynamic cutoffs of cardiac index (CI <2.2 L/min per m2), pulmonary capillary wedge pressure (>18 mm Hg), right atrial pressure (>8 mm Hg), and mean pulmonary artery pressure (≥25 mm Hg or pulmonary hypertension) with the combined end point of cardiac transplant/left ventricular assist device and death and heart failure admissions separately was assessed. A total of 469 CA patients underwent right heart catheterization (light chain CA=42% and transthyretin CA=52%) of whom 69%, 64%, and 79% had elevated right atrial pressure, pulmonary capillary wedge pressure, and pulmonary hypertension, respectively. The classic hemodynamic cutoffs for right atrial pressure (hazard ratio, 1.26 [0.98-1.62]) and mean pulmonary artery pressure (hazard ratio, 1.28 [0.96-1.71]) did not identify patients at higher risk for adverse outcome; however, cutoffs of 14 mm Hg for right atrial pressure (hazard ratio, 1.59 [1.26-2.00]) and 35 mm Hg for mean pulmonary artery pressure (hazard ratio, 1.30 [1.01-1.66]) performed better to detect worse outcome (P<0.05 for both). Reduced CI occurred in 55% of patients and was the strongest variable associated with the risk for cardiac transplant/left ventricular assist device and death, heart failure admissions, and reduced functional capacity. Reduced CI independently predicted risk on top of the Mayo-score in light chain CA and National Amyloid Center score in transthyretin CA (P<0.05 for both). Patients with light chain CA had higher pulmonary capillary wedge pressure and lower stroke volume index but maintained CI through a higher heart rate. Hemodynamic variables are grossly abnormal in CA, but elevated filling pressures are prognostic at significantly higher threshold values than classic cutoff values. CI is the hemodynamic variable most strongly associated with outcome and functionality in CA.

Prevalence and prognosis of cardiac amyloidosis in patients who underwent diphosphonate scintigraphy for non-cardiological reasons

Transthyretin cardiac amyloidosis is a rare and currently underdiagnosed disease. Untreated, median survival since diagnosis is estimated to be between 3 and 5 years. Diphosphonate scintigraphy is one of the earliest positive examinations well before biological or clinical signs. The objective of this study is to determine the prevalence of cardiac involvement in patients who underwent disphophonate scintigraphy for non-cardiological reasons and to follow their prognosis. Our study is a retrospective, descriptive, monocentric study carried out at the university hospital of Poitiers. Collection of all scintigraphy with Technetium 99m-labelled disodium Hydroxymethylene Diphosphonate (HMDP-99mTc), performed at the Poitiers University Hospital between January 1, 2006 and January 1, 2012. 725 patients were included and all scintigraphy were reanalyzed and we retained only the Perugini 2 and 3 stage for the diagnosis of amyloidosis. The study focuses on the prevalence and the overall and detailed mortality of these patients at 5 years. In all, 20 scintigraphy showed Perugini scores of 2 or 3, i.e., a prevalence of about 1% in the study. The prevalence by age group was also studied: there is an age-related gradient: among patients over 70 years of age, it is calculated at 2.7% (20/725 patients); among patients over 80 years of age, it is calculated at 4.4% (14/316) (Fig. 1); and among patients over 90 years of age, it is calculated at 16.7% (4/24). No fixation was found in patients under 70-years-old. The overall 5-year mortality rate was calculated at 85%, the majority of which was due to cancer. The discovery of Perugini stage 2 and 3 cardiac staining on scintigraphy for non-cardiological reasons among the 725 patients analyzed is uncommon (1%). There is an age-related prevalence gradient (up to 16.7% over 90 years). Radiologists should refer patients to amyloidosis specialists for specific management, which would allow amyloidosis to be managed at an early stage to probably decrease hospitalizations and mortality.

Validation of Amylo-AFFECT, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis

Validation of Amylo-AFFECT, a self-reported questionnaire to assess health-related quality of life and to determine the prognosis in cardiac amyloidosis

Multimodality Imaging in Cardiac Amyloidosis.

Cardiac amyloidosis is an increasingly recognized condition with a growing range of targeted therapies, but diagnosis requires a high index of suspicion and multimodality imaging expertise. Early diagnosis remains key to improving quality of life and survival. This article reviews the multimodality imaging approach to the diagnosis, differentiation, and prognosis of cardiac amyloidosis. Recent advances in multimodality cardiac imaging have allowed for earlier diagnosis of cardiac amyloidosis resulting in earlier initiation of life-saving therapy in cases of light chain amyloidosis and life-prolonging therapy in transthyretin amyloidosis. With these advances in multimodality imaging, it is important for cardiologists and cardiac imagers to be aware of the subtleties of early disease, the appropriate diagnostic approach as well as understanding the practicalities and pitfalls that are encountered with each modality.

Diagnostic Value of Extracellular Volume Quantification and Myocardial Perfusion Analysis at CT in Cardiac Amyloidosis.

Background CT can provide information regarding myocardial perfusion and expansion of the extracellular space, which is relevant to patients with cardiac amyloidosis (CA). Purpose To evaluate the role of CT in the diagnosis and prognosis of CA. Materials and Methods In this prospective study (Commission National de l'Informatique et des Libertés registration no. 1431858), participants with CA, participants with nonamyloid cardiac hypertrophy (NACH), and participants without hypertrophy were included between April 2017 and December 2018. The confirmed diagnosis of CA was determined according to established criteria (ie, proven with positive bone scintigraphy or endomyocardial biopsy). All participants were imaged with dynamic CT perfusion imaging at whole-heart cardiac CT. Extracellular volume measured at CT and myocardial perfusion parameters calculated on CT perfusion maps were compared among different participant groups. Differences between continuous data were tested using the unpaired t test, Mann-Whitney rank-sum test, or the Kruskal-Wallis test. Results A total of 84 participants with CA, 43 participants with NACH, and 33 participants without hypertrophy were included. Participants with CA exhibited a higher value of extracellular volume measured at CT (mean, 54.7% ± 9.7 [standard deviation]) than participants with NACH (mean, 34.6% ± 9.1; P < .001) and participants without hypertrophy (mean, 35.9% ± 9.9; P = .001). Mean myocardial blood volume and mean myocardial blood flow were lower in participants with CA (mean myocardial blood volume: 4.05 mL/100 g of myocardium ± 0.80; mean myocardial blood flow: 73.2 mL/100 g of myocardium per minute ± 25.7) compared to participants with NACH (mean myocardial blood volume: 5.38 mL/100 g of myocardium ± 1.20, P < .001; mean myocardial blood flow: 89.6 mL/100 g of myocardium per minute ± 31.3, P = .007) and participants without hypertrophy (mean myocardial blood volume: 5.68 mL/100 g of myocardium ± 1.05; mean myocardial blood flow: 106.3 mL/100 g of myocardium per minute ± 29.8; P < .001 for both). Extracellular volume measured at CT (hazard ratio >0.56 vs ≤0.56 = 4.2 [95% CI: 1.4, 11.8]), mean slope (hazard ratio ≤3.0 sec-1 vs >3.0 sec-1 = 0.2 [95% CI: 0.1, 0.8]), and time to peak (hazard ratio >20 seconds vs ≤20 seconds = 11.6 [95% CI: 1.3, 101.6]) were predictive of mortality in participants with CA. Conclusion Participants with cardiac amyloidosis exhibited an increase in extracellular volume at CT and abnormal CT perfusion parameters. Extracellular volume and several perfusion parameters were predictive of mortality. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Zimmerman in this issue.

Les amyloses cardiaques

Different types of amyloid deposits involve the heart. Transthyretin and light chain amyloidosis are the most frequent. Diagnostic performance, typing and treatments have improved in the last decade, and prognosis of cardiac amyloidosis is now significantly better thanks to targeted therapies. In this article, we will describe the clinical manifestations of cardiac amyloidosis, the diagnostic approach and detail the characteristics and specific treatments of the most frequent types of cardiac amyloidosis. We will focus on the histopathological aspects, especially on the importance of amyloid typing.

Trends in Diagnostic Imaging of Cardiac Amyloidosis: Emerging Knowledge and Concepts.

Cardiac amyloidosis (CA) has long been recognized as a rare disease. However, recent advances in cardiac imaging have led to increased identification of hidden CA in patients diagnosed with heart failure. This shift suggests that the actual incidence of CA is underestimated. The prognosis of CA is generally poor, especially in patients with advanced heart failure. However, recent developments in therapeutic interventions have improved the survival of patients with CA. An early diagnosis and interventions involving effective therapies are essential contributors to improved prognoses. Recent noninvasive diagnostic imaging modalities such as echocardiography, cardiac MRI, and nuclear imaging have facilitated the precise and early diagnosis of CA and enabled the initiation of appropriate management. The authors present an updated review of the clinical features of CA, including a discussion of current trends in noninvasive diagnostic imaging. ©RSNA, 2020.

Outcome of Cardiac Light-Chain Amyloidosis in the Era of Novel Therapy - A Single-Center Cohort Study of 227 Patients.

Cardiac involvement occurs in more than half of the patients with light-chain amyloidosis (AL), but the characteristics, treatment and prognosis of cardiac AL (CAL) are not fully described. Methods and Results: A total of 227 patients with CAL diagnosis between January 2009 and March 2017 at Peking Union Medical College Hospital were included. Patients with Mayo stages I, II and III AL accounted for 0.9%, 49.8% and 49.3%, respectively. Autologous stem cell transplantation, bortezomib combinations, non-bortezomib regimens and palliative treatment were given as first line therapy in 3.1%, 44.1%, 30.8% and 22.0% of patients, respectively. Overall hematological response and cardiac response were achieved in 60.6% and 37.2% of evaluable patients, respectively. The median overall survival (OS) was 17 months in all patients, and 10 months in those with Mayo stage III. In patients with Mayo stage III disease who survived for >1 month, the bortezomib group survived significantly longer than the non-bortezomib group (median OS, not reached vs. 12 months, P=0.019). Three independent prognostic factors for survival were identified: N-terminal fragment of B-type natriuretic peptide (NT-proBNP) ≥5,000 pg/mL, bone marrow plasma cells ≥10%, and systolic blood pressure <100 mmHg. CAL patients had poor prognosis, but those treated with bortezomib combinations had a better outcome than the non-bortezomib group.

Role of cardiovascular imaging for the diagnosis and prognosis of cardiac amyloidosis

Cardiac amyloidosis (CA) describes the pathological process of amyloid protein deposition in the extracellular space of the myocardium. Unfortunately, the diagnosis of CA is often made late and when the...

Usefulness of T2 ratio in the diagnosis and prognosis of cardiac amyloidosis using cardiac MR imaging.

To detect if a difference of T2 ratio, defined as the signal intensity (SI) of the myocardium divided by the SI of the skeletal muscle on T2-weigthed cardiac magnetic resonance (CMR) imaging, exists between patients with systemic amyloidosis, by comparison to control subjects. To determine if a relationship exists between T2 ratio and the overall mortality. CMR imaging examinations of 73 consecutive patients (48 men, 25 women; mean age, 63 years±15[SD]) with amyloidosis and suspicion of CA and 27 control subjects were retrospectively analyzed after institutional review board approval. Final diagnosis of CA was retained in case of histological confirmation of CA, typical pattern of CA on imaging and/or positivity of 99Technetium-hydroxymethylene diphosphonate scintigraphy. Patients were divided in 2 groups according to the presence or the absence of CA. T2 ratios were calculated in patients with and those without CA and in control subjects with using analysis of variance. Prognostic value of T2 ratio was studied with a Kaplan-Meier curve. Thirty-five patients (51%) had CA and 33 (49%) were free from CA. T2 ratio was lower in patients with CA (1.18±0.29) than in patients without cardiac involvement (1.37±0.35) (P=0.03) and control subjects (1.45±0.24) (P=0.004). A T2 ratio of 1.36 was the best threshold value for predicting CA with a sensitivity of 63% and a specificity of 73%. Kaplan-Meier analysis showed a significant relationship between a shortened overall survival and a T2 ratio<1.36. Patients with CA exhibit lower T2 ratio on CMR imaging by comparison with patients free of CA and control subjects.

Abstract 18563: The Role of a Change in ECG Voltage on the Diagnosis and Prognosis in Cardiac Amyloidosis

Background: Low voltage on ECG may be caused by various medical conditions. In cardiac amyloidosis, low voltage in the limb leads is found in approximately 50% with AL and only 20-25% of ATTR, whether senile or familial. Despite not meeting low voltage criteria on ECG, a reduction of voltage over time may signify amyloid cardiomyopathy. Methods: The electrocardiograms of consecutive patients at the time of a diagnosis of cardiac amyloidosis at our institution were analyzed. Patients with ventricular paced rhythms were excluded. An additional ECG at least one year prior to the diagnosis was also analyzed. The sum of voltage in all limb leads and the Sokolow voltage (S wave in V1 plus R wave in V5 or V6) index were calculated. Low limb voltage was defined as ≤ 5 mm in all limb leads and low precordial voltage as ≤ 10 mm in all precordial leads. A Cox proportional hazards model was used to assess the correlation between decreasing ECG voltage and 3 year mortality. Results: A total of 338 patients (192 AL, 146 ATTR, age 68.7 +/- 12.1 years, obese 57%, HTN 54%) were identified. At the time of diagnosis, 167 patients (49.4%) met either low limb or low precordial voltage criteria. The limb lead voltage decreased in 63 of 73 patients (86.3%) and the Sokolow voltage decreased in 62 of 73 patients (84.9%). The mean overall decrease in limb lead voltage was 10.6 +/- 12.6 mm overall or 3.3 +/- 4.6 mm per year. The Sokolow voltage decreased 6.5 +/- 7.1 mm overall or 1.8 +/- 2.3 mm per year. On univariable analysis, the annualized decrease in Sokolow voltage showed a non-significant trend towards an increase in mortality. Conclusion: A decrease in voltage on serial ECG’s is more prevalent than low voltage in cardiac amyloidosis. There is a trend towards increased mortality in patients who have a greater decrease in voltage over time. The evaluation of serial ECG’s for changes in voltage is important to recognize in the diagnosis of cardiac amyloidosis and may have prognostic value.

Usefulness of 99mTc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis

Results CA was diagnosed in all AL (n=14) and wt-TTR (n=21). Among m-TTR (n=34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. 99mTc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two, and in one AL. A visual score ≥2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic, and scintigraphic variables, NYHA III-IV and HR/SR>1.94 predicted acute heart failure and/or death.

Usefulness of 99mTc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis

Background: Amyloidosis is characterized by extracellular deposits of insoluble proteins that cause tissue damage. The three main types are monoclonal light chain (AL), wild-type transthyretin (wt-TTR) and mutated transthyretin (m-TTR) amyloidosis. Cardiac amyloidosis (CA) raises diagnostic challenges.Objective: To assess the diagnostic accuracy of 99mTc-HMDP-scintigraphy for typing CA, differentiating CA from non-amyloid left ventricle hypertrophy (LVH), and predicting outcomes.Methods: 121 patients with suspected CA underwent 99mTc-HMDP-scintigraphy in addition to standard investigations.Results: CA was diagnosed in all AL (n = 14) and wt-TTR (n = 21). Among m-TTR (n = 34), 26 had CA, 4 neuropathy without CA and 4 were asymptomatic carriers. Of the 52 patients with non-amyloid heart disease, 37 had LVH and served as controls. 99mTc-HMDP cardiac uptake occurred in all wt-TTR, in m-TTR with CA except two and in one AL. A visual score ≥ 2 was 100% specific for diagnosing TTR-CA. Among TTR-CA, heart-to-skull retention (HR/SR) correlated with CA severity (LVEF and NT-proBNP). Median follow-up was 111 days (50;343). In a multivariate Cox model including clinical, echocardiographic and scintigraphic variables, NYHA III-IV and HR/SR > 1.94 predicted acute heart failure and/or death.Conclusions: This preliminary study suggests that 99mTc-HMDP-scintigraphy may aid differentiation between transthyretin and AL-CA as well as CA from other LVHs. 99mTc-HMDP-scintigraphy appears to provide prognostic information in CA.