Light-chain Cardiac Amyloidosis Research Articles

Oxidative damage in immunoglobulin light chain and transthyretin cardiac amyloidosis – a closer look

Heart failure is a progressive disease, representing a growing cause of morbidity, hospitalization, and mortality. An increasingly common type of heart failure with preserved ejection fraction (HFpEF) is an immunoglobulin light chain and transthyretin cardiac amyloidosis, in the pathophysiology of which oxidative damage appears to exert a strong impact. Reactive oxygen and nitrogen species have physiological signaling functions, but their overaccumulation, as in cardiac amyloidosis, leads to cardiomyocyte damage and apoptosis, and to cardiac hypertrophy and fibrosis. Moreover, such pathological processes worsen the redox damage with the perpetuation of an inflammatory state, in a vicious cycle. Here, the role of oxidative damage in the transthyretin and immunoglobulin light chain cardiac amyloidosis, the underlying pathogenic mechanisms, the therapeutic implications, and possible future strategies are reviewed.

Outcomes of Modified Mayo Stage IIIa and IIIb Cardiac Light-Chain Amyloidosis: Real-World Experience in Clinical Characteristics and Treatment-67 Patients Multicenter Analysis.

Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light chains in various organs. One of the most common organs involved in AL is the heart, with 50-70% of patients clinically symptomatic at diagnosis. We conducted a multi-center, retrospective analysis of 67 patients diagnosed between July 2012 and August 2022 with the European 2012 modification of Mayo 2004 stage III cardiac AL. The most important factors identified in the univariate Cox analysis contributing to a longer OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1, New York Heart Association functional classification (NYHA FC) ≤ 2, the use of autologous stem cell transplantation (ASCT) after induction treatment, achieving a hematological response (≥very good partial response) and cardiac (≥partial response) response after first-line treatment. The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment.

A Novel Approach to Cardiac Magnetic Resonance Scar Characterization in Patients Affected by Cardiac Amyloidosis: A Pilot Study.

Background and Objectives: Cardiac magnetic resonance (CMR) imaging has become an essential instrument in the study of cardiomyopathies; it has recently been integrated into the diagnostic workflow for cardiac amyloidosis (CA) with remarkable results. An additional emerging role is the stratification of the arrhythmogenic risk by scar analysis and the possibility of merging these data with electro-anatomical maps. This is made possible by using a software (ADAS 3D, Galgo Medical, Barcelona, Spain) able to provide 3D heart models by detecting fibrosis along the whole thickness of the myocardial walls. Little is known regarding the applications of this software in the wide spectrum of cardiomyopathies and the potential benefits have yet to be discovered. In this study, we tried to apply the ADAS 3D in the context of CA. Materials and Methods: This study was a retrospectively analysis of consecutive CMR imaging of patients affected by CA that were treated in our center (Marche University Hospital). Wherever possible, the data were processed with the ADAS 3D software and analyzed for a correlation between the morphometric parameters and follow-up events. The outcome was a composite of all-cause mortality, unplanned cardiovascular hospitalizations, sustained ventricular arrhythmias (VAs), permanent reduction in left ventricular ejection fraction, and pacemaker implantation. The secondary outcomes were the need for a pacemaker implantation and sustained VAs. Results: A total of 14 patients were deemed eligible for the software analysis: 8 patients with wild type transthyretin CA, 5 with light chain CA, and 1 with transthyretin hereditary CA. The vast majority of imaging features was not related to the composite outcome, but atrial wall thickening displayed a significant association with both the primary (p = 0.003) and the secondary outcome of pacemaker implantation (p = 0.003). The software was able to differentiate between core zones and border zones of scars, with the latter being the most extensively represented in all patients. Interestingly, in a huge percentage of CMR images, the software identified the highest degree of core zone fibrosis among the epicardial layers and, in those patients, we found a higher incidence of the primary outcome, without reaching statistical significance (p = 0.18). Channels were found in the scar zones in a substantial percentage of patients without a clear correlation with follow-up events. Conclusions: CMR imaging plays a pivotal role in cardiovascular diagnostics. Our analysis shows the feasibility and applicability of such instrument for all types of CA. We could not only differentiate between different layers of scars, but we were also able to identify the presence of fibrosis channels among the different scar zones. None of the data derived from the ADAS 3D software seemed to be related to cardiac events in the follow-up, but this might be imputable to the restricted number of patients enrolled in the study.

Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introduction and objetivesCardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n = 109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n = 87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p = 0.029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p = 0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p = 0.021). ConclusionsCA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

Outpatient management of patients with cardiac light chain amyloidosis

Outpatient management of patients with cardiac light chain amyloidosis

Prognostic mortality factors in advanced light chain cardiac amyloidosis: A prospective cohort study.

Predicting mortality in severe AL cardiac amyloidosis is challenging due to elevated biomarker levels and limited thresholds for stratifying severe cardiac damage. This prospective, observational, cohort study included de novo, confirmed cardiac AL amyloidosis patients at the Henri Mondor National Reference Centre. The goal was to identify predictors of mortality to enhance prognostic stratification and improve informed decision-making regarding therapy. Over the 12-year study period, among the 233 patients included, 133 were NYHA III-IV and 179 Mayo 2004 III. The independent predictors for mortality identified were hsTnT, NT-proBNP, cardiac output, and conjugated bilirubin. A novel prognostic, conditional stratification, Mondor amyloidosis cardiac staging (MACS) was developed with biomarker cut-off values for Stage 1: hsTnT≤107ng/L and NT-proBNP≤3867ng/L (n=77; 33%); for stage 2 NT-proBNP>3867ng/L (n=72; 30%). For stage 3, if troponin >107ng/L, regardless of NT-proBNP then CB 4μmol/L, was added (n=41; 17.5%) and stage 4: CB>4μmol/L (n=43; 18.5%). The median overall survival was 8months 95% CI [2-24]. At 1year, 102 (44%) patients died and the Kaplan-Meier median survival with MACS Stage 1 was not reached, while stage 2 was 15.2months (95% CI [11-18]) and stage 3, 6.6months (95% CI [1-13]). Notably, among European stage II patients, 17.1%, n=8 were MACS stage 3 and European stage IIIb 21.4% (n=23) were MACS stage 4. Importantly, among European stage IIIb patients 42.2% (n=29) were classified MACS stage 4 and 12.5% n=9 were only MACS stage 2. The Mondor prognostic staging system, including conjugate bilirubin may significantly improve prognostic stratification for patients with severe cardiac amyloidosis.

Prognostic implications of premature ventricular contractions and non-sustained ventricular tachycardia in light-chain cardiac amyloidosis.

Premature ventricular contractions (PVC) and non-sustained ventricular tachycardia (NSVT) are commonly observed in light chain cardiac amyloidosis (AL-CA), but their association with prognosis is still unclear. We aimed to evaluate the prognostic value of PVCs and NSVT in patients with moderate-to-advanced AL-CA. We retrospectively included patients with AL-CA at modified 2004 Mayo stages II-IIIb between February 2014 and December 2020. Twenty-four-hour Holter recordings were assessed on admission. The outcomes included (i) new onset of adverse ventricular arrhythmia (VA) or sudden cardiac death (SCD) and (ii) cardiac death during follow-up. Of the 143 patients studied (60.41 ± 11.06 years, male 64.34%), 132 (92.31%) had presence of PVC, and 50 (34.97%) had NSVT on Holter. Twelve (8.4%) patients died in hospital and 131 patients were followed up (median 24.4 months), among whom 71 patients had cardiac death, and 15 underwent adverse VA/SCD. NSVT [hazard ratio (HR): 13.57, 95% confidence interval (CI): 3.06-60.18, P < 0.001], log-transformed PVC counts (HR: 1.46, 95%CI: 1.15-1.86, P = 0.002) and PVC burden (HR: 1.43 95%CI:1.14-1.80, P = 0.002) were predictive of new onset of adverse VA/SCD. The highest tertile of PVC counts (HR: 2.33, 95%CI: 1.27-4.28, P = 0.006) and PVC burden (HR: 2.58, 95%CI: 1.42-4.69, P = 0.002), rather than NSVT (HR: 1.16, 95%CI: 0.67-1.98, P = 0.603), was associated with cardiac death. Higher PVC counts/burden provided incremental value on modified 2004 Mayo stage in predicting cardiac death, with C index increasing from 0.681 to 0.712 and 0.717, respectively (P values <0.05). PVC count, burden, and NSVT significantly correlated with adverse VA/SCD during follow-up in patients with AL-CA. Higher PVC counts/burdens added incremental value for predicting cardiac death.

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.

Relative apical sparing obtained with speckle tracking echocardiography is not a sensitive parameter for diagnosing light-chain cardiac amyloidosis.

Distinguishing light-chain cardiac amyloidosis (AL CA) from left ventricular wall thickening (LVWT) resulted from other etiologies has proven to be challenging. This study aimed to determine the sensitivity and specificity of relative apical sparing in diagnosing AL CA and investigate the differences in clinical and echocardiographic characteristics between AL CA patients with apical sparing and those with non-apical sparing. A total of 63 consecutive patients with AL CA, 102 consecutive patients with LVWT (including 51 hypertrophic cardiomyopathy (HCM) and 51 hypertension) and 33 healthy individuals were recruited retrospectively at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Conventional and speckle tracking echocardiography were performed on all subjects. Although wall thickening was observed in all patients, almost all functional parameters were worse in AL CA, except for relative apical longitudinal strain (LS) (P=0.906). Of 63 patients with AL CA, only 17.5% (n=11) showed an apical sparing pattern. Patients with apical sparing had poorer cardiac performance than those with non-apical sparing. Relative apical sparing showed the lowest diagnostic accuracy with an area under the curve (AUC) of 0.58 [95% confidence interval (CI): 0.49-0.67, sensitivity: 17.5%, specificity: 98.0%, P=0.095] to detect AL CA, but right ventricular strain (RVS) (AUC: 0.86, P<0.001) showed the highest among all echocardiographic parameters. When diagnosing AL CA patients with non-apical sparing, RVS continued to maintain excellent diagnostic accuracy (AUC: 0.84, P<0.001), followed by left atrial reservoir strain (LASr) (AUC: 0.77, P<0.001). The diagnostic value of relative apical sparing for AL CA was limited with low sensitivity. In clinical practice, the diagnosis of early AL CA patients should not solely rely on relative apical sparing.

A new staging system using right atrial strain in patients with immunoglobulin light-chain cardiac amyloidosis.

There are minimal data on the prognostic impact of right atrial strain during the reservoir phase (RASr) in patients with immunoglobulin light-chain (AL) cardiac amyloidosis. Among 78 patients who were diagnosed with AL cardiac amyloidosis at Kumamoto University Hospital from 2007 to 2022, 72 patients with sufficient two-dimensional speckle tracking imaging data without chemotherapy before the diagnosis were retrospectively analysed. During a median follow-up of 403days, 31 deaths occurred. Age and the rate of male sex were not significantly different between the all-cause death group and the survival group (age, 70.4±8.8years vs. 67.0±10.0years, P=0.14, male sex, 65% vs. 66%, P=0.91). The estimated glomerular filtration rate (eGFR) was significantly lower, and B-type natriuretic peptide (BNP) and high sensitivity cardiac troponin T (hs-cTnT) were significantly higher, in the all-cause death group versus the survival group (eGFR, 48.2±21.0mL/min/1.73m2 vs. 59.4±24.4mL/min/1.73m2 , P<0.05, BNP, 725 [360-1312] pg/mL vs. 123 [81-310] pg/mL, P<0.01, hs-cTnT, 0.12 [0.07-0.18] ng/mL vs. 0.05 [0.03-0.08] ng/mL, P<0.01). Left ventricular (LV) global longitudinal strain (GLS) (LV-GLS), left atrial strain during the reservoir phase (LASr), right ventricular GLS (RV-GLS), and RASr were significantly lower in the all-cause death group versus the survival group (LV-GLS, 8.5±4.3% vs. 11.8±3.8%, P<0.01, LASr, 8.8±7.1% vs. 14.3±8.1%, P<0.01, RV-GLS, 11.6±5.1% vs. 16.4±3.9%, P<0.01, RASr, 10.2±7.3% vs. 20.7±9.5%, P<0.01). RASr was significantly associated with all-cause death after adjusting for RV-GLS, LV-GLS and LASr (hazard ratio [HR]: 0.91, 95% confidence interval [95% CI]: 0.83-0.99, P<0.05). RASr and log-transformed BNP were significantly associated with all-cause death after adjusting for log-transformed troponin T and eGFR (RASr, HR: 0.93, 95% CI: 0.87-1.00, P<0.05; log-transformed BNP, HR: 2.10, 95% CI: 1.17-3.79, P<0.05). The optimal cut-off values were RASr: 16.4% (sensitivity: 66%, specificity: 84%, area under curve [AUC]: 0.81) and BNP: 311.2pg/mL (sensitivity: 83%, specificity: 78%, AUC: 0.82) to predict all-cause mortality using ROC analysis. Kaplan-Meier analysis revealed that patients with low RASr (<16.4%) or high BNP (>311.2pg/mL) had a significantly high probability of all-cause death (both, P<0.01). We devised a new staging score by adding 1 point if RASr decreased or BNP levels increased more than each cut-off value. The HR for all-cause death using score 0 as a reference was 5.95 (95% CI: 1.19-29.79; P<0.05) for score 1 and 23.29 (95% CI: 5.37-100.98; P<0.01) for score 2. The new staging system using RASr and BNP predicted prognosis in patients with AL cardiac amyloidosis.

Conduction disturbance followed by progressive ventricular wall thickening as an initial manifestation of light-chain cardiac amyloidosis.

Conduction disturbance followed by progressive ventricular wall thickening as an initial manifestation of light-chain cardiac amyloidosis.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis

To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40%≤LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

Light-Chain Cardiac Amyloidosis: Cardiac Magnetic Resonance for Assessing Response to Chemotherapy.

Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.

Left ventricular myocardial work improves in response to treatment and is associated with survival among patients with light chain cardiac amyloidosis.

Complete haematologic response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function and better outcomes. We sought to evaluate the effect of response to treatment for AL-CA on echocardiographic indices of myocardial deformation and work and their prognostic significance. Sixty-one patients treated for AL were enrolled and underwent echocardiographic assessment at baseline and at 1 year. Patients were stratified according to haematologic response as complete or not complete responders. A significant reduction in median N-terminal pro-brain natriuretic peptide (NT-proBNP) (2771-1486 pg/mL; P < 0.001) and posterior wall thickness (13-12 mm; P = 0.002) and an increase in global work index (GWI) (1115-1356 mmHg%; P = 0.018) was observed at 1 year. Patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2-12.0 mm; P = 0.006), improved global longitudinal strain (GLS) (-11.6 to -13.1%; P for interaction = 0.045), increased global constructive work (1245-1436 mmHg%; P = 0.008), and GWI (926-1250 mmHg%, P = 0.002) compared with non-CR. Furthermore, deltaGLS (ρspearman = 0.35; P < 0.001) and deltaGWI (ρspearman = -0.32; P = 0.02) correlated with delta NT-proBNP. Importantly, patients with GLS and GWI response had a better prognosis (log-rank P = 0.048 and log-rank P = 0.007, respectively). After adjustment for Mayo stage, gender, and response status, deltaGLS [hazard ratio (HR) = 1.404, P = 0.046 per 1% increase] and deltaGWI (HR = 0.996, P = 0.042 per 1mmHg% increase) were independent predictors of survival. Complete haematologic response to treatment is associated with improved left ventricular myocardial work indices, and their change is associated with improved survival in AL-CA.

Chinese consensus on the diagnosis and treatment of immunoglobulin light-chain cardiac amyloidosis.

Chinese consensus on the diagnosis and treatment of immunoglobulin light-chain cardiac amyloidosis.

Remarkable and Prolonged Response to Melphalan and High-Dose Dexamethasone Combined Therapy of a Patient with Light-Chain Cardiac Amyloidosis

Remarkable and Prolonged Response to Melphalan and High-Dose Dexamethasone Combined Therapy of a Patient with Light-Chain Cardiac Amyloidosis

Speckle Tracking Echocardiography for the Diagnosis and Prognosis of Light Chain Cardiac Amyloidosis

Background Cardiac amyloidosis was thought to be a rare disease, but the data shows that its prevalence rate is increasing, and the light chain (AL) cardiac amyloidosis are the most common and worst [1]. Because of the lack of symptoms specificity in the preliminary stages of AL cardiac amyloidosis, resulting in underdiagnosis or severe delays in diagnosis, patients are often delayed in the optimal timing of treatment. A considerable proportion of patients are diagnosed after the onset of symptoms of heart failure which progresses rapidly and results in poor prognosis and high mortality. Patients have a mortality rate of up to 50% within 4-6 months after diagnosis of congestive heart failure and the median survival of these patients were less than 12 months [2]. Therefore, early diagnosis and treatment are particularly important for them. Speckle tracking echocardiography has a good imaging analysis of cardiac amyloidosis, which remains the most often used imaging tool. This study aimed to explore the use of speckle tracking echocardiographic parameters to build models which improve the diagnostic rate of patients with suspected AL cardiac amyloidosis and assess the prognosis of patients with AL cardiac amyloidosis. Methods We studied twenty-four patients of pathologically confirmed amyloidosis from March 2017 to February 2023 at the First Affiliated Hospital of Soochow University. According to the criteria for organ involvement, patients were divided into two groups based on whether the heart was involved or not and SPSS 26.0 was used to analyze data. The differences of characteristics and various parameters of Speckle tracking echocardiography between two groups were compared and the indicators with statistical difference were selected for single factor analysis and multivariate analysis. Statistically significant factors were used to establish diagnosis and prognosis assessment models as below. Result In this study, the rate of cardiac involvement was 62.5%. Until June 30 th, 2023, median follow-up time of twenty-four patients was 31 months, and the 5-year survival rate was 74% in CA group and 85.7% in non-CA group. Characteristics The results showed that CA group has lower baseline blood pressure, and the levels of NT-pro BNP and dFLC were significantly higher in the CA group compared to the non-CA group. In speckle tracking echocardiography parameters, CA group has significantly increased IVSd, LVPWd, RWT, E/e and decreased EF, interventricular septum e', lateral wall e' and left ventricular global strain. Diagnosis The results showed that CA group is more likely to be involved in the heart when monoclonal proteins are formed in the peripheral blood （OR=0.031, 95%CI 0.003-0.365, P=0.002）. In univariate analysis, E/e&amp;gt;10.85, interventricular septum e‘&amp;lt;5.25 cm/s, lateral wall e‘&amp;lt;6.05 cm/s, |left ventricular global strain|&amp;lt;16.3% and left ventricular diastolic function ≥Class II have the effect on CA group with statistically significant. Incorporating them into variables to construct a multivariate logistic regression model showed that: the model was built successfully (Omnibus test: P&amp;lt;0.001) and the goodness of fit model is well (Hosmer-Leme show test: P=1). 88.9% of the study subjects who were CA patients were predicted by the model to be CA patients, while 92.9% of the study subjects who were not CA patients were predicted by the model to be not CA patients, but the 5 factors had no significant effect on cardiac amyloidosis (P &amp;gt; 0.05). Prognosis assessment The result of the study shows that IVPWd&amp;gt;13.5mm, RWT&amp;gt; 0.51, NT pro-BNP&amp;gt;6614pg/mL and dFLC&amp;gt;142.35mg/L are elevated risk factors for prognosis with statistically significant. (Figure1). They were included in the variables to construct a multi-factor Cox proportional hazards model and it turns out: the model was built successfully (Omnibus test: P&amp;lt;0.05), but these 4 factors had no significant effect on cardiac amyloidosis (P &amp;gt; 0.05). Conclusion Speckle tracking echocardiography is of great value in the diagnosis and prognosis of patients with cardiac amyloidosis. The combined analysis of echocardiography parameters and serological abnormalities can help in the diagnosis and prognostic assessment of the disease, it also helps to identify patients with poor prognosis early and increasing the possibility of future treatment strategies based on risk stratification.

Serial 18F-Florbetaben Positron Emission Tomography and Cardiac Magnetic Resonance Imaging in the Evaluation of Systemic Light Chain Cardiac Amyloidosis Enhances Diagnostic and Response Assessment Accuracy

Background: There is a need for improved assessment of cardiac involvement in systemic amyloidosis by non-invasive methods to increase accuracy of diagnosis and to assist with monitoring and prognostication of the condition. We have previously shown that 18F-florbetaben, a novel amyloid binding radiotracer, can identify the presence of cardiac amyloid in positron emission tomography (PET/CT) imaging. We aim to evaluate the role of imaging with 18F-florbetaben PET/CT, cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) in the initial diagnosis and response assessments of patients with light chain (AL) cardiac amyloidosis (AL-CA). Methods: Twelve patients diagnosed with systemic AL amyloidosis and proven or suspected cardiac involvement, between June 2018 and December 2020, were prospectively recruited to undergo 18F-florbetaben PET/CT, CMR and TTE imaging prior to commencement and 6 months post systemic therapy. 40-minute dynamic and static PET/CT images were acquired following 18F-florbetaben radiotracer injection. Left ventricular myocardial standardised uptake values (SUV) were recorded and used to graph time activity curves (TAC). Percentage myocardial tracer retention (MTR) was derived from the dynamic data. CMR was performed using a 3.0T MRI system. The Modified Look-Locker Inversion recovery (MOLLI) method was utilized to generate native and gadolinium-enhanced T1 mappings, which were then used to calculate the global extracellular volume (ECV). PET and CMR indices were compared to 2D-speckled TTE metrics and cardiac biomarkers (BNP, cTnI) using Pearson Correlation for statistical analysis. Overall survival was calculated using the Kaplan-Meir method. Results: Participant characteristics were as per table 1. Five deaths occurred during the study, all due to progressive AL amyloidosis; with 4 of these occurring prior to the planned second imaging timepoint. Two-year survival was 58.3%, with a mean overall survival of 7.3 years (95% CI 4.08 - 10.52). All patients had a baseline PET/CT; 8 were able to have a concurrent CMR. The remaining 4 were unable have a CMR due to incompatible devices or were clinically unwell at the time. Seven patients went on to have a repeat PET/CT and 5 had comparative CMR imaging 6 months after commencing treatment. Baseline 18F-florbetaben PET/CT scans demonstrated characteristic AL-CA patterns of prolonged myocardial tracer retention TAC in 10 out of the 12 patients (Figure 1). Patients' 8 and 12 TACs (highlighted with arrows in Figure 1) did not follow the usual AL-CA MTR pattern and their MTRs were calculated to be below a previously defined threshold of ≥40% for the presence of cardiac amyloid. This prompted review of the diagnosis of AL-CA in these patients and both were found to have alternative causes for the TTE and cardiac biomarker abnormalities which were initially interpreted as AL-CA. Analysis of the different imaging metrics showed significant correlation between MTR and ECV (r=0.575; p=0.04) as well as ECV and GLS (r=0.62; p=0.024). ECV also correlated with BNP (r=0.637; p=0.019) as did GLS and BNP (r=0.678; p=0.002). There was no association between MTR and cardiac biomarkers. 8 patients were assessable at the 6-month timepoint; only 1 patient had a cardiac response at 6 months by the International Society of Amyloidosis (ISA) criteria and they demonstrated a &amp;gt;10% reduction in MTR on follow-up PET/CT. Two patients had stable cardiac disease as per ISA criteria: 1 had &amp;gt;10% reduction in MTR and went on to achieve subsequent cardiac response without further therapy; the other had an increase in MTR by 18.5% and went on to salvage ASCT for suboptimal haematological and cardiac responses (partial remission and stable organ disease). Four patients had cardiac progression by ISA criteria with a worsening of MTR by at least 15% (mean=19.1%). Conclusion: Patients with AL-CA display prolonged 18F-florbetaben retention on PET/CT imaging which also appears useful to exclude the presence of cardiac amyloidosis in patients with co-existent cardiac conditions. Preliminary data supports the role of 18F-florbetaben PET/CT in cardiac response assessment, but further studies are required to determine the optimal timing of follow up imaging, which is likely to be beyond the 6-month time point, and to determine clinically significant MTR ranges for monitoring and prognostication.

Effects of treatment response on echocardiographic features among patients with light-chain cardiac amyloidosis

Abstract Background Complete response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function. The aim of this study was to evaluate the effect of treatment for AL-CA on echocardiographic characteristics of patients, and the prognostic impact of changes in longitudinal strain and myocardial work. Methods The study population comprised of sixty-one patients treated for AL between 2020 and 2022. All patients underwent comprehensive echocardiographic assessment including longitudinal strain and myocardial work imaging at baseline and at 1-year follow-up. Patients were stratified according to the depth of hematologic response to treatment for AL-CA as complete or not complete responders. The relationship between echocardiographic parameters and all-cause mortality was assessed by Kaplan Meir curves and cut-off points were selected using ROC analysis. Results A significant reduction in median NT-proBNP (from 2,771 to 1,486 pg/mL; p&amp;lt;0.001), posterior wall thickness (PWT) (from 13 to 12mm; p=0.002), and an increase in global work index (GWI) (from 1,115 to 1,356 mmHg%; p=0.018) was observed in all patients at 1-year follow up. After stratifying patients based on hematologic response to treatment, patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2 to 12.0mm; p=0.006), a trend towards improved global longitudinal strain (GLS) (-11.6 to -13.1%; p=0.064) and increased global constructive work (1,245 to 1,436 mmHg%; p=0.008), in addition to significant improvements in NT-proBNP, posterior wall thickness and global work index. Furthermore, the delta GLS (ρspearman=0.35; p&amp;lt;0.001) and delta GWI (ρspearman=-0.32; p=0.02) significantly correlated with delta NT-proBNP. Patients with GWI response, either any response or ROC-curve derived cut-off, had a better prognosis compared with patients without GWI response (log-rank p=0.043 and log-rank p=0.035, respectively). Conclusions Among patients treated for AL-CA, those with hematologic CR exhibited significant improvement in GWI and GWW. Additionally, our results indicate that GLS and GWI may have prognostic value in predicting survival among AL-CA patients and their changes correlate to NTproBNP decrease.

Temporal trends and outcomes of heart failure patients between light-chain cardiac amyloidosis and transthyretin cardiac amyloidosis: insights from the national inpatient sample database

Abstract Background Systemic amyloidosis comprises a family of diseases caused by deposition of misfolded fibrillar proteins in the extracellular space. Cardiac involvement is the leading cause of morbidity and mortality in systemic amyloidosis and a major determinant of survival, regardless of the underlying pathogenesis of amyloid production. Data regarding the clinical outcomes in immunoglobulin light-chain (AL) va amyloid transthyretin (ATTR) cardiac amyloidosis (CA) is scarce. Purpose We aimed to investigate the trends, baseline clinical characteristics, and clinical outcomes of AL CA vs ATTR CA in heart failure (HF) patients. Methods Data from United States National Inpatient Sample database from 2017-2020 was used to identify hospitalizations for CA with concurrent cardiomyopathy in HF patients and were further subclassified into AL vs ATTR CA. Outcomes were compared using univariate and multivariate logistic regression analysis. Results During 2017-2020, there were 12430 hospitalizations of CA of which 96.3% were ATTR CA and 3.7% were AL CA. Patients with ATTR-CA when compared to AL-CA were older, predominantly male, more blacks, and had a higher prevalence of co-morbidities including atrial arrythmias, sick sinus syndrome, and aortic stenosis. Patients with AL CA had significantly increased in-hospital mortality, length of stay, total charges, acute heart failure exacerbations, and cardiopulmonary resuscitation. After adjustment for baseline characteristics, AL CA patients had significantly increased odds of in-hospital mortality and HF hospitalizations when compared to ATTR CA cohort. There is an increasing trend in hospitalizations in AL CA from 2017-2019. Conclusion AL cardiac amyloidosis had significantly higher odds of in-hospital mortality and HF hospitalizations in comparison to ATTR cardiac amyloidosis cohort. AL CA had lower incidence of stroke, thromboembolism and major bleeding with similar need for cardiac device implantation.Figure 1Figure 2