Cardiac AL Amyloidosis Research Articles

Cardiac transthyretin amyloidosis in patients with conduction system disease

Abstract Background/Introduction Cardiac amyloidosis (CA) is characterized by extracellular deposition of misfolded proteins in the heart. The data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. More than 98% of currently diagnosed cardiac amyloidosis result from fibrils consisting of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR). The natural history of ATTR cardiomyopathy commonly includes both the conduction system disease and arrhythmias, which may occur years before the onset of heart failure. Conduction abnormalities are commonly encountered among patients with CA and constitute an important cause of morbidity and mortality. Most reports agree that pacemakers are most common in wild type ATTR-CA, followed by hereditary ATTR-CA and, finally, AL-CA. Purpose As unexplained LV wall thickness ≥ 12 mm is a screening sign of possible cardiac ATTR, systematicscreening for CA in patients requiring permanent pacemakers with unexplained LV wall thickness of ≥ 12 mm seems to be rational and could possibly lead to early diagnosis of cardiac ATTR. To the best of our knowledge, the usefulness of such screening has not been investigated before. This project, therefore, aims to determine the prevalence of cardiac ATTR and its subtypes in this preselected group, and to propose the most suitable battery of diagnostic procedures for this purpose. Methods Population to be tested: Consecutive patients ≥50 years referred for permanent pacemaker implantation with unexplained LV wall thickness ≥12 mm determined by echocardiography. The research protocol was that of an open-label prospective study. Biochemistry samples including serum troponin I and NT-proBNP were collected before pacemaker implantation. All patients were screened for ATTR-CA according to the recommendations of the Position statement of the ESC Working group on myocardial and pericardial diseases. Tc-DPD scintigraphy scan served as a gold standard for determining the diagnosis of cardiac ATTR. Results Out of 100 consecutive patients meeting inclusion criteria, 15 % suffered from amyloidosis (12 patients were diagnosed with ATTR and 3 with AL cardiac amyloidosis). Table 1 shows a variety of parameters, many of which differed between patient groups with and without amyloidosis, confirming the wide range of parameters significantly associated with cardiac amyloidosis; our ongoing research in this field could lead to the development of a scoring system for detection of cardiac amyloidosis. Conclusions The prevalence of cardiac amyloidosis in the investigated group was 15 %. Systematic screening for ATTR in patients with unexplained LV wall thickness ≥ 12 mm requiring permanent pacemaker implantation seems to be rational and could possibly lead to an earlier diagnosis of cardiac amyloidosis, especially ATTR.

Arterial-myocardial coupling in primary AL amyloidosis. A validation study of vascular involvement

Abstract Background Primary AL amyloidosis is a rare yet lethal systemic disorder. Previously published own and others’ work indicated that vascular involvement in AL cardiac amyloidosis defined as low blood pressure or paradoxical vasodilation may independently affect survival. Mechanistic data will pave the way to validate the clinical role of vascular involvement in these patients. Purpose We sought to explore the presence of arterial-myocardial coupling in AL amyloidosis by investigating associations between markers of vascular and cardiac involvement. Methods We consecutively recruited n=152 newly diagnosed patients with AL amyloidosis that underwent thorough vascular examination including reactive vasodilation (flow mediated vasodilation, FMD and vasodilation in response to cold-pressor test) using high resolution ultrasonography. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) and aortic pressures and markers of arterial wave reflections were estimated using radial artery tonometry. In a subgroup of patients, transthoracic echocardiography (n=152) and cardiac magnetic resonance (CMR) (n=59) were performed. Results Vascular reactivity correlated with global longitudinal strain (GLS), left ventricle ejection fraction (LVEF)/GLS ratio and worse LV volumes. Vasodilation post-cold pressure test was correlated with LV mass. cSBP exhibited a negative correlation with markers of heart involvement, wall thickness markers, GLS, and CMR tissue characterization markers. A positive correlation between cSBP and LVEF, rotation and twist strain, myocardial work and contractility markers and late gadolinium enhancement (LGE). cDBP was associated with systolic function and contractility markers, with myocardial work indices and LGE. A negative relationship with GLS, LA strain, RV GLS and LA diameter and E/e’ was noted. In addition, T2 was negatively correlated with cDBP. SBP was correlated positively with LVEF, contractility markers, and LGE myocardium and negatively correlated with biomarkers of heart involvement, GLS, CMR structure and tissue characterization. DBP was positively correlated with LGE and myocardial work. A negative relation with NTproBNP, E/e’, RVSP, LA diameter and T2 mapping was noted. Time of wave reflections (Tr) was negatively correlated with rotation strain and positively correlated with circumferential strain, LA strain and LV structure. Ai@75 was positively correlated with myocardial work and contractility markers, and LGE. Ai@75 was negatively correlated with markers of heart involvement, LV structure, E/e’, worse GLS and adverse CMR tissue characterization. Conclusion Markers of peripheral vascular dysfunction were associated with cardiac structure and function acquired both with echocardiography and CMR in AL amyloidosis. This arterial-myocardial coupling supports the clinical role of peripheral vascular involvement in this disease and warrants further investigation.

Artificial intelligence (AI)-enhanced electrocardiography: a machine-learning model for differential diagnosis between hypertrophic cardiomyopathy, cardiac amyloidosis and Anderson-Fabry disease

Abstract Background The differential diagnosis between Hypertrophic Cardiomyopathy (HCM) and phenocopies is challenging and relies on a comprehensive approach, which includes clinical and instrumental data, as well as laboratory exams and genetic testing. In this setting, 12-lead electrocardiogram (ECG) represents a valuable tool, but although typical patterns have been described, their diagnostic ability to discriminate between different etiologies is limited and requires considerable clinical experience. However, a correct diagnosis is of pivotal importance, allowing the prompt initiation of phenotype-specific therapies and consequently improving patient survival. Purpose Aim of this study was to develop a machine-learning model based on human-based ECG features to support the differential diagnosis between HCM, Cardiac Amyloidosis (CA) and Anderson-Fabry Disease (AFD). Methods We retrospectively examined ECGs of 200 patients, 50 affected by HCM, 100 affected by CA (50 AL CA and 50 transthyretin CA) and 50 with a diagnosis of AFD cardiomyopathy. The patients were then divided in sinus rhythm (SR) subgroup (158 patients) and atrial fibrillation (AF) subgroup (42 patients). For each subgroup, patients were randomly split into a training (80%) and a testing cohort (20%), and a random forest (RF) model was trained on the training cohort, with hyperparameter tuning via 10-fold cross validation. The resulting model was then tested on the testing cohort to assess its predictive accuracy. Results Both RF models (SR and AF) showed good discriminative performance in this multiclass classification task on the testing cohort [SR: accuracy 67%; multiclass area under the curve (AUC) 0.797, 95% confidence interval (CI) 0.472 -0.827; AF: accuracy 75%; multiclass AUC 0.792, 95% CI 0.349 – 0.968]. Figure 1 and figure 2 report for each model the rank of the most important variables for class prediction. Conclusions An AI-based ECG interpretation based on human-derived ECG features can predict the etiology underlying an hypertrophic phenotype, helping to perform a correct diagnosis and consequently to set a specific therapeutic process.

Incidence and predictors of sudden death in patients with cardiac amyloidosis

Introduction Although sudden death (SD) is a recognized complication of cardiac amyloidosis, there is scarce data about its incidence, mechanisms, and predictors. The aim of this study was to describe incidence of SD and to analyze possible risk factors. Methods Consecutive patients with ATTR or AL cardiac amyloidosis evaluated at two European centers were identified. SD was defined as unexpected death in clinically stable patients. Cox proportional hazard regression was performed to assess risk factors in univariate analysis. Those statistically significant were then assessed through age-adjusted multivariate analysis. Results Analysis included 784 patients, 569 with ATTR amyloidosis (mean age 74.1 ± 12.1 years) and 215 with AL amyloidosis (mean age 64.5 ± 10.8 years). After a median follow-up of 1.9 years, SD rate at 2 years was 1.8% in ATTR. Previous pacemaker implantation (PPM) was associated with increased risk after age-adjusted analysis (HR 4.97; 95%CI: 1.39–17.7; p = 0.01). SD rate in AL amyloidosis patients at 2 years was 8.0% after a median follow-up of 1.2 years. Betablockers and NYHA III-IV were independently associated with an increased risk after age-adjusted multivariate analysis (HR 7.06 95%CI (2.31–21.5) p = 0.001) and (HR 4.56 95%CI (1.51–13.8) p = 0.007) respectively. Conclusions SD is more frequent in AL than in ATTR cardiac amyloidosis. SD is associated with different risk factors in both entities.

Prognostic value of CMR-derived extracellular volume in AL amyloidosis: a multicenter study

Background This study aimed to assess the prognostic value of cardiac magnetic resonance (CMR) variables and compare them with biological and echocardiographic markers in patients with AL cardiac amyloidosis (CA). Methods We conducted a prospective study across three tertiary centres, where patients underwent clinical examination, blood tests, echocardiography, and CMR. The primary endpoint was all-cause mortality. Results A total of 176 patients with AL CA were included, with a median age of 68 years (IQR 58-75). According to the 2004 Mayo Clinic staging, 121 patients (69%) were in stage 3. During a median follow-up of 22 months (IQR 8–48), 45 patients died, and 55 were hospitalized for heart failure. Patients who died had higher NT-proBNP and troponin levels, and lower LVEF, cardiac output, and longitudinal strain. Among CMR variables, extracellular volume (ECV) was most strongly associated with all-cause mortality. In multivariate Cox models, including Mayo Clinic staging, ECV ≥ 0.45 was independently associated with mortality (HR 2.36, CI 95% 1.47–5.60) and also with heart failure hospitalizations (HR 4.10, 95%CI 2.15–8.8). Conclusion ECV is a powerful predictor of outcomes in AL CA, providing additional prognostic value on top of Mayo Clinic staging.

Doxycycline Plus Bortezomib-Containing Regimens for the Treatment of Light-Chain Amyloidosis in the Frontline Setting: Experience from the Amyloidosis Program of Calgary.

Background: Pre-clinical and retrospective data suggest that doxycycline added to treatment regimens has benefit in AL amyloidosis. However, a recent multicenter, open-label, randomized controlled trial in AL amyloidosis patients treated with CyBorD did not demonstrate a progression-free survival (PFS) or cardiac PFS benefit with added doxycycline. Objective: The main objective of this study was to explore the role of doxycycline combined with bortezomib-containing regimens (BCRs) for newly diagnosed AL amyloidosis patients with cardiac involvement and to compare them with a cohort of concurrent patients treated with BCR only. Material and Methods: AL amyloidosis patients, newly diagnosed between January 2012 and March 2022, who were treated with BCR at the Amyloidosis Program of Calgary (APC) were evaluated. Results: Sixty-four concurrent patients were identified. Thirty-nine patients received doxycycline in addition to BCR (BCR-D) for a median of 8 months. The overall response rate was similar among the groups. No significant differences in VGPR/CR, dFLC at 1 month, time to first response, time to best response, or organ responses were noted between the BCR alone and BCR-D groups. Summary and Conclusions: Our retrospective study demonstrated that doxycycline combined with BCR failed to prolong OS, PFS, or cardiac responses compared with BCR alone in patients with cardiac AL amyloidosis.

Dexamethasone for the Treatment of Cardiac Al Amyloidosis: A Case Report and Literature Review

Background: Systemic immunoglobulin light chain (AL) amyloidosis is a condition characterised by the conversion of light chains (LCs) from their soluble states into highly organised fibrillar aggregates that deposit in tissues, resulting in progressive organ damage and dysfunction. While previously considered incurable, treatment strategies are emerging for cardiac amyloidosis, underscoring the importance of early diagnosis. Case Summary: We present the case of a 69-year-old male patient who was admitted with acute onset of dyspnea and diagnosed with heart failure. The diagnosis of cardiac amyloidosis was made on the basis of a discrepancy between the results of the electrocardiogram and the echocardiogram, a conclusion that was further substantiated by the use of scintigraphy and myelogram. Given the poor left ventricular fraction, the standard chemotherapy regimen was replaced with corticosteroid therapy, which led to a significant improvement within the first 48 hours, unfortunately reversible with rapid clinical deterioration followed by sudden death within a week. Conclusion: Our aim is to highlight that early administration of dexamethasone is associated with significant clinical improvement but a high mortality rate in patients with AL cardiac amyloidosis.

Post-COVID Myocarditis in Patients with Primary Cardiomyopathies: Diagnosis, Clinical Course and Outcomes.

The aim of this study was to evaluate the clinical course and outcomes of post-COVID myocarditis in patients with cardiomyopathies (CMP). This case series includes 10 patients with different CMPs who had COVID-19 (seven men; 48.4 ± 11.4 yr.): left ventricular non-compaction (n = 2), arrhythmogenic right ventricular CMP in combination with a heterozygous form of hemochromatosis (n = 1, HFE), restrictive CMP (n = 1, MyBPC3), laminopathy (n = 1, LMNA), dilated cardiomyopathy (n = 1, MYH7 + MyBPC3), Danon's disease (n = 1, LAMP2) and AL cardiac amyloidosis (n = 3). Myocardial morphological examination with immunohistochemical staining and PCR for SARS-CoV-2 and cardiotropic viruses was performed in six patients, while cardiac MRI and anti-cardiac antibody titres were evaluated in all patients. Post-COVID lymphocytic myocarditis was confirmed morphologically in six patients (with LVNC, RCM, ARCV, Danon's disease, and AL amyloidosis). Spike and nucleocapsid coronavirus proteins were detected in cell infiltrates, endothelium and cardiomyocytes in all biopsies; SARS-CoV-2 RNA was found in five out of six. In four patients, the diagnosis of myocarditis was based on MRI, high titres of anti-cardiac antibodies and clinical data. The mean time from COVID-19 to the diagnosis of myocarditis was 7 (5; 10.5) months. Myocarditis manifested with the onset/increase of arrhythmias and heart failure. Immunosuppressive therapy with corticosteroids was administered to six patients and led to an increase in ejection fraction and improvement of heart failure symptoms in five of them. CMPs are a favourable background for the development of post-COVID myocarditis. The onset or deterioration of heart failure and/or arrhythmias in patients with CMPs after COVID-19 requires the exclusion of myocarditis and, if present, the administration of immunosuppressive therapy.

Advances in Diagnosis and Treatment of AL Cardiac Amyloidosis

Advances in Diagnosis and Treatment of AL Cardiac Amyloidosis

Prognostic Value of Serum Galectin-3 for Survival in Patients with Cardiac Light-Chain Amyloidosis.

Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis. A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates. The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan-Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; p = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017-5.910, p = 0.046). This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.

Light chain mutations contribute to defining the fibril morphology in systemic AL amyloidosis

Systemic AL amyloidosis is one of the most frequently diagnosed forms of systemic amyloidosis. It arises from mutational changes in immunoglobulin light chains. To explore whether these mutations may affect the structure of the formed fibrils, we determine and compare the fibril structures from several patients with cardiac AL amyloidosis. All patients are affected by light chains that contain an IGLV3-19 gene segment, and the deposited fibrils differ by the mutations within this common germ line background. Using cryo-electron microscopy, we here find different fibril structures in each patient. These data establish that the mutations of amyloidogenic light chains contribute to defining the fibril architecture and hence the structure of the pathogenic agent.

Right Ventricular Strain Improves the Echocardiographic Diagnosis and Risk Stratification of Transthyretin Cardiac Amyloidosis Among Other Phenotypes of Left Ventricular Hypertrophy

Cardiac amyloidosis is a diffuse disease affecting all cardiac chambers. The value of right ventricular free-wall strain is uncertain as an echocardiographic red flag. We hypothesized that right ventricular free-wall strain is of added value for diagnostic and prognostic purposes in patients with transthyretin cardiac amyloidosis (ATTR-CA). A diagnosis of ATTR-CA required positive Tc-99m pyrophosphate scintigraphy and negative serum clonal dyscrasia. Patients with left ventricular (LV) hypertrophy (LVH; interventricular septal thickness ≥1.2cm) by echocardiography and negative pyrophosphate scintigraphy served as controls after exclusion of amyloid light-chain cardiac amyloidosis. Longitudinal strain was computed with speckle-tracking echocardiography. We studied 108 subjects with ATTR-CA and 106 controls with LVH, retrospectively. Right ventricular free-wall strain was independently associated with the diagnosis of ATTR-CA after adjusting for classical echocardiographic parameters, namely, relative apical sparing (RAS), e', and E/e'. Right ventricular free-wall strain≥-16% was incremental to LV RAS in the overall group and in the subgroup without extreme wall thickness (≤1.4cm; Harrell's C, net reclassification improvement=0.213, P<.001; and net reclassification improvement= 0.463, P=.015, respectively). Major adverse cardiovascular and cerebrovascular events (heart failure hospitalization, stroke, death) occurred in 47 ATTR-CA patients, during follow-up (median, 38; range, 6-60months). Right ventricular free-wall strain≥-16% was associated with 3-fold increased risk of MACCE in ATTR-CA patients independently of age, comorbidities, B-type natriuretic peptide, and tafamidis treatment. Right ventricular free-wall strain was additive to LV ejection fraction for risk stratification (chi square =10.2; P=.017). Right ventricular free-wall strain>-16% has incremental value to LV RAS for the differential diagnosis of ATTR-CA among LVH phenotypes and is associated with poor prognosis.

Long-term outcomes after cardiac transplantation in AL amyloidosis.

7572 Background: Systemic AL amyloidosis can lead to progressive multi-organ dysfunction including advanced heart failure which may require orthotopic heart transplantation (OHT). Hematologic outcomes of AL amyloidosis post-OHT are not well described. Methods: We report outcomes for patients with AL amyloidosis with cardiac involvement post-OHT from Nov 2008 - Jun 2023 at Vanderbilt University Medical Center. Hematologic response was graded per the ISA guidelines. Results: Fourteen pts underwent OHT of whom 13 had lambda light chain disease. Three (21%) pts had isolated AL amyloidosis (AL) without myeloma (MM), while 11 (79%) also had MM: 6 with bone marrow plasma cells (BMPCs) 10-19% (AL-PCMM-10) and 5 with BMPC ≥20% (AL-PCMM-20). One each with AL-PCMM-10 and AL-PCMM-20 had lytic lesions (AL-CRAB). Median age at OHT was 55.5 yrs (range 37-74). Median time from diagnosis to OHT was 18 mo (range 3-62). Five (35%) pts had biopsy-proven extracardiac amyloid involvement. Median difference in serum free light chains at first evaluation was 70 mg/dL (range 9-289). Three pts were Mayo 2012 stage II, 4 stage III, and 7 stage IV. Four pts had t(11;14) and 1 had 1q gain. Ten (71%) pts received triplet therapy (VCd or VRd) and 3 (21%) received quadruplet therapy (Dara-VCd or Isa-VCd) pre-OHT. Six (43%) pts had autologous stem cell transplantation (ASCT); 1 pre-OHT and 5 post-OHT. Of ASCT pts, 1 pt achieved CHR, 1 VGPR, 2 PR, and 1 had PD pre-ASCT. Pre-OHT, 4 pts achieved CHR, 6 VGPR, 3 PR, and 1 had PD. Eleven pts (79%) received maintenance therapy post-OHT (5 proteosome inhibitors, 6 anti-CD38). At last follow-up, 8 pts were in CHR, 3 in VGPR, 1 in PR, and 2 had PD. Four (29%) pts died post-OHT: 2 from AL recurrence (1 each with AL and AL-PCMM-10), 1 from cardiac allograft vasculopathy (AL-CRAB), and 1 from renal failure (AL-CRAB). Three (21%) pts had hematologic relapse 5, 21 and 48 mo post-OHT, and of those, 2 had recurrent cardiac amyloid in graft 37 and 71 mo post-OHT. Of those with hematologic relapse, 2 had AL-PCMM-10 and 1 had AL. One pt had post-transplant lymphoproliferative disorder 126 mo post-OHT, requiring treatment. Median follow-up and survival of the cohort post-OHT was 2.25 yrs (range 0.5-13.8). Conclusions: In this single-center analysis of pts undergoing OHT for cardiac AL amyloidosis, we demonstrate feasibility of excellent long-term outcomes, in predominantly high-risk AL pts where majority harbored high-risk disease with MM overlap, either by AL-CRAB or AL-BMPC. Induction alone led to ≥VGPR response in 10 (71%) pts pre-OHT and further therapy deepened this to 11 (79%) pts. Both AL-CRAB pts died during follow-up, highlighting the overall poor prognosis in this specific subgroup. In our cohort, non-relapse related mortality was seen in only 2 (14%) pts, demonstrating acceptable post-OHT risk and overall ability to achieve far improved outcomes in the high-risk cardiac AL amyloidosis patient population that otherwise suffers from rapid and universal mortality.

The Real-World Data on Patients With Cardiac Stage IIIb AL Amyloidosis

BackgroundMorbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, but the real-world data on these patients is still limited. Patients and MethodsA retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients. ResultsThe median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure. ConclusionThe hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.

Cardiac amyloidosis in India: Experience from a single tertiary care center

Abstract PURPOSE: Cardiac amyloidosis (CA) is perceived as a rare disease. Identifying certain red flag signs in patients helps in early diagnosis of CA. Epidemiology of CA in India is not well known. We performed this study to determine various demographic, clinical, and imaging parameters of patients diagnosed with CA in a tertiary care center in India. METHODS: We prospectively screened 48 patients between January 2021 and December 2023 with one or more red flags signs of CA. Their demographic, clinical, and imaging parameters were analyzed. RESULTS: Among 48 patients with one or more red flag signs, CA was diagnosed in 23 patients (47.91%). Seventeen patients were found to have AL CA and 6 had ATTR CA. The mean age of patients was 62.2 years with slight male preponderance (n = 13, 56.5%). All the patients presented with heart failure with the majority in New York Heart Association Class III (n = 11, 47.8%). The most common electrocardiogram abnormality was low-voltage QRS complexes in limb leads (56.5% of patients). Common echocardiographic abnormalities were left ventricular hypertrophy (100%), biatrial enlargement (100%), and reduced global longitudinal strain with relative apical sparing (cherry on top appearance) (74%). Tc99-PYP bone scintigraphy was done in 16 patients. It showed grade 2 uptake in all ATTR CA patients and 6 out of 11 in AL CA patients.Cardiovascular magnetic resonance was done in 5 AL CA patients. The most typical finding was diffuse subendocardial late gadolinium enhancement. CONCLUSIONS: There are significant lacunae in epidemiologic, diagnostic, and prognostic data of CA, especially in India. CA is not as uncommon, as it was perceived earlier. High index of suspicion with the use of novel echocardiographic parameters can identify patients who require further testing to confirm CA. Early diagnosis of CA helps in the early initiation of disease-modifying therapy which improves survival.

(1157) - Shifting Strategies: Heart Transplant as a Bridge to Chemotherapy in Cardiac Al Amyloidosis

(1157) - Shifting Strategies: Heart Transplant as a Bridge to Chemotherapy in Cardiac Al 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.

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.

Prognostic value of native T1 and extracellular volume in patients with immunoglubin light-chain amyloidosis

BackgroundCardiac involvement in patients with immunoglubin light-chain amyloidosis (AL) is a major determinant of treatment choice and prognosis, and early identification of high-risk patients can initiate intensive treatment strategies to achieve better survival. This study aimed to investigate the prognostic value of native T1 and ECV in patients with AL-cardiac amyloidosis (CA).MethodsA total of 38 patients (mean age 59 ± 11 years) with AL diagnosed histopathologically from July 2017 to October 2021 were collected consecutively. All patients were performed 3.0-T cardiac magnetic resonance (CMR) including cine, T1 mapping, and late gadolinium enhancement (LGE). Pre- and post-contrast T1 mapping images were transferred to a dedicated research software package (CVI42 v5.11.3) to create parametric T1 and ECV values. In addition, clinical and laboratory data of all patients were collected, and patients or their family members were regularly followed up by telephone every 3 months. The starting point of follow-up was the time of definitive pathological diagnosis, and the main endpoint was all-cause death. Kaplan-Meier analysis and Cox proportional risk model were used to evaluate the association between native T1 and ECV and death in patients with CA.ResultsAfter a median follow-up of 27 (16, 37) months, 12 patients with CA died. Kaplan-Meier analysis showed that elevated native T1 and ECV were closely associated with poor prognosis in patients with CA. The survival rate of patients with ECV > 44% and native T1 > 1389ms were significantly lower than that of patients with ECV ≤ 44% and native T1 ≤ 1389ms (Log-rank P < 0.001), and was not associated with the presence of LGE. After adjusting for clinical risk factors and CMR measurements in a stepwise multivariate Cox regression model, ECV [risk ratio (HR):1.37, 95%CI: 1.09–1.73, P = 0.008] and native T1 (HR:1.01, 95%CI: 1.00-1.02, P = 0.037) remained independent predictors of all-cause mortality in patients with CA.ConclusionsBoth native T1 and ECV were independently prognostic for mortality in patients with CA, and can be used as important indicators for clinical prognosis assessment of AL.

Assessment of Tp-Te interval in patients with cardiac AL amyloidosis.

Prolonged Tp-Te interval is strongly associated with fatal ventricular arrhythmias and mortality. This association has been demonstrated in various diseases. However, the current literature does not give any information on Tp-Te interval in cardiac amyloid light-chain (AL) amyloidosis. We retrospectively screened 116 cardiac AL amyloidosis patients and 35 patients were included in the study. Demographic, laboratory, 12-lead electrocardiographic (QTc, Tp-Te V1-V6) and transthoracic echocardiographic data of the patients were analysed and compared with 35 healthy controls. QTc and Tp-Te V2-V5 were significantly prolonged in the cardiac AL amyloidosis group (p < 0.05). Also, there was a positive and statistically significant correlation between the parameters of QTc and Tp-Te V3-V6, and also between the parameters of interventricular septum thickness at enddiastole and Tp-Te V2-V5. We present the first strong evidence of prolonged Tp-Te intervals in patients with cardiac AL amyloidosis. There may also be a relationship between prolonged Tp-Te interval and the development of arrhythmia in this patient group, as in some other groups. There is a need for prospective studies examining the relationship of prolonged Tp-Te interval with arrhythmias and its prognostic significance in cardiac AL amyloidosis.