Diagnostic score of cardiac involvement in AL amyloidosis

Abstract Aims Early diagnosis of cardiac involvement is a key issue in the management of AL amyloidosis. Our objective was to establish a diagnostic score of cardiac involvement in AL amyloidosis and to compare it with the current consensus criteria [i.e. left ventricular hypertrophy >12 mm and N-terminal pro b-type natriuretic peptide (NT-proBNP) >332 ng/L]. Methods and results We carried out a prospective and multicenter study on AL amyloidosis patients who underwent cardiac evaluation including clinical examination, electrocardiography (ECG), cardiac biomarkers, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (CMR). Cardiac involvement was based on CMR and/or endomyocardial biopsy. In a derivation cohort of 114 patients (82 with cardiac involvement), the highest diagnostic accuracy was observed with NT-proBNP and troponin blood levels, TTE-derived global longitudinal strain (LS), and apical to basal LS gradient. By using multivariate analysis, we established a diagnostic score including global LS ≥−17% (1 point), apical/(basal + median) LS ≥0.90 (1 point), and troponin T >35 ng/L (1 point). A score >1 was associated with sensitivity of 94% and specificity of 97%, an area under the curve of 0.98 [95% confidence interval (CI) 0.93–0.99] as well as a net reclassification index of 0.39 (95% CI 0.28–0.46) when compared with consensus criteria. In a validation cohort of 73 AL amyloidosis patients, the area under the receiver operating characteristic curve of the diagnostic score was 0.97 (95% CI 0.90–0.99). Conclusion Combining T troponin blood levels and two echo-derived strain parameters leads to very high accuracy for diagnosing cardiac involvement in AL amyloid patients.

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Assessment of disease severity and outcome in patients with systemic light-chain amyloidosis by the high-sensitivity troponin T assay

Blood ◽

10.1182/blood-2010-02-267708 ◽

2010 ◽

Vol 116 (14) ◽

pp. 2455-2461 ◽

Cited By ~ 67

Author(s):

Arnt V. Kristen ◽

Evangelos Giannitsis ◽

Stephanie Lehrke ◽

Ute Hegenbart ◽

Matthias Konstandin ◽

...

Keyword(s):

Light Chain ◽

Cardiac Involvement ◽

Troponin T ◽

Interventricular Septum ◽

High Sensitivity ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Blood Levels ◽

Al Amyloidosis ◽

Light Chain Amyloidosis

Abstract Cardiac biomarkers provide prognostic information in light-chain amyloidosis (AL). Thus, a novel high-sensitivity cardiac troponin T (hs-TnT) assay may improve risk stratification. hs-TnT was assessed in 163 patients. Blood levels were higher with cardiac than renal or other organ involvement and were related to the severity of cardiac involvement. Increased sensitivity was not associated with survival benefit. Forty-seven patients died during follow-up (22.3 ± 1.0 months). Nonsurvivors had higher hs-TnT than survivors. Outcome was worse if hs-TnT more than or equal to 50 ng/L and best less than 3 ng/L. Survival of patients with hs-TnT 3 to 14 ng/L did not differ from patients with moderately increased hs-TnT (14-50 ng/L), but was worse if interventricular septum was more than or equal to 15 mm. Discrimination according to the Mayo staging system was only achieved by the use of the hs-TnT assay, but not by the fourth-generation troponin T assay. Multivariate analysis revealed hs-TnT, NT-proBNP, and left ventricular impairment as independent risk factors for survival. hs-TnT and NT-proBNP predicted survival, even after exclusion of patients with impaired renal function. Plasma levels of the hs-TnT assay are associated with the clinical, morphologic, and functional severity of cardiac AL amyloidosis and could provide useful information for clinicians on cardiac involvement and outcome.

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Maximal Stress Ergometry Performance is Associated with Troponin T and Abdominal Aortic Calcification Score in Severe Chronic Kidney Disease

10.21203/rs.3.rs-74844/v1 ◽

2020 ◽

Author(s):

Roosa Lankinen ◽

Markus Hakamäki ◽

Kaj Metsärinne ◽

Niina S Koivuviita ◽

Jussi P Pärkkä ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Troponin T ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Aortic Calcification ◽

Cardiac Biomarkers ◽

Abdominal Aortic Calcification ◽

Abdominal Aortic ◽

Calcification Score

Abstract Background Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied. Methods 174 CKD 4-5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments. Results The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e’ and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (β= -0.09, p=0.02), AAC (β= -1.67, p<0.0001) and diabetes (β= -11.07, p<0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model. AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectivelyConclusions TnT and AAC are independent determinants of maximal ergometry stress test workload in patients with advanced CKD.http://www.ClinicalTrials.gov NCT04223726

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Serum biomarkers for detection of cardiomyopathy in survivors of childhood cancer: A report from the St. Jude Lifetime Cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e21526 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e21526-e21526

Author(s):

Stephanie Dixon ◽

Carrie R. Howell ◽

Lu Lu ◽

Kirsten K. Ness ◽

Juan Plana ◽

...

Keyword(s):

Childhood Cancer ◽

Troponin T ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

New Onset

e21526 Background: Childhood cancer survivors are at increased risk for cardiovascular morbidity and mortality. Little is known about the utility of cardiac biomarkers (NT-proBNP, cardiac troponin-T [TnT]) for long-term surveillance. Methods: Cross-sectional analyses of 1213 survivors ≥18 years of age and ≥10 years from cancer diagnosis (786 exposed to cardiotoxic therapy [174 radiation therapy (RT) alone, 366 anthracycline alone, 246 both] and 427 unexposed). TnT > 0.01 ng/ml and NT-proBNP levels > 97.5th percentile age- and sex-specific cutoffs were considered abnormal. Three-dimensional left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diastolic function and cardiomyopathy (CM) according to the CTCAE v4.03 were evaluated. Generalized linear models estimated risk ratios (RR) and 95% confidence intervals (CI). Results: Among survivors (median 8.7 [range 0.0-23.6] years at diagnosis; 35.5 [range 19.1-62.2] years at evaluation), NT-proBNP and TnT were abnormal in 22.5% and 0.4%, respectively. A dose-dependent increased risk for abnormal NT-proBNP was seen with exposure to chest RT (referent no RT, 1- < 20 Gy RR 1.62 [CI 1.07-2.46], 20- < 30 Gy RR 1.68 [1.23-2.30], ≥30 Gy RR 3.66 [2.89-4.64]; p for trend < 0.0001) and anthracycline (referent no anthracycline, 1-200mg/m2 RR 1.39 [1.01-1.91], 201-350mg/m2 RR 2.28 [1.74-2.99], > 350mg/m2 RR 2.99 [2.27-3.95]; p for trend < 0.0001). Survivors with CM at the time of evaluation had abnormal NT-proBNP (grade 2 CM RR 1.46, CI 1.08-1.99; grade 3-4 CM 2.66, 2.02-2.39). However, among exposed survivors previously undiagnosed with clinical CM, NT-proBNP had poor sensitivity and moderate specificity in identifying those with new onset of abnormal LVEF ( < 53%), GLS or diastolic dysfunction: sensitivity (29%, 30%, 33%), specificity (75%, 77%, 76%). Also, 132 (20.2%) had abnormal NT-proBNP with normal LVEF (≥53%). Conclusions: Abnormal NT-proBNP levels were prevalent and associated with prior cardiotoxic therapy and established CM but were not sensitive for detection of new onset CM. Longitudinal follow-up is needed to determine whether abnormal NT-proBNP in the large number of survivors without CM is predictive of future CM.

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Randall-type monoclonal immunoglobulin deposition disease: description of cardiac involvement

European Heart Journal ◽

10.1093/ehjci/ehaa946.2140 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Ramonatxo ◽

R Garcia ◽

F Joly ◽

B Degand ◽

N Bidegain ◽

...

Keyword(s):

Heart Disease ◽

Mayo Clinic ◽

Cardiac Involvement ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Basement Membranes ◽

Al Amyloidosis ◽

Monoclonal Immunoglobulin ◽

Amyloid Heart Disease ◽

Heavy Chains

Abstract Background Randall-type monoclonal immunoglobulin disease (MIDD) is a rare complication of a monoclonal plasma cell clone. MIDD differs from AL amyloidosis by the presence of Congo red negative non-organized immunoglobulin (Ig) deposits, most commonly light chains (LCDD) along basement membranes and sometimes heavy chains (HCDD) or light and heavy chains (LHCDD). As AL amyloidosis MIDD is a multi-systemic disease, and affects the heart. To date no study has focused on the clinical characteristics of heart disease in MIDD. Purpose The aim of this study was to describe the cardiologic features of patients with biopsy-proven MIDD and suspected cardiac involvement. Methods This multi-center, nation-wide retrospective study extracted from the database of the French reference center for AL amyloidosis and other Ig deposition diseases between 2012 to 2019. Diagnosis of cardiac involvement was assessed according to the International Society of Amyloidosis criteria for amyloid heart disease, as follows: left ventricular hypertrophy with a diastolic septum thickness ≥12mm, NTproBNP serum level ≥332 ng / L, histological evidence on cardiac or extra cardiac biopsy of typical linear non-organized Ig deposits along basement membranes. Severity was defined according to the Mayo Clinic classification for AL amyloidosis. Results Among 20 patients included (mean age was 70±9 years), 11 (55%) were males; 13 (65%) were LCDD, 3 (15%) HCDD and 4 (20%) LHCDD. At diagnosis, 19 (95%) had a history of hypertension, 3 (16%) had atrial fibrillation, 3 (15%) had NYHA grade 3 or 4 dyspnea. Mayo Clinic score was stage 3a in 4 patients (20%) and stage 3b in 6 patients (30%). The most frequent ECG changes were microvoltage (40%) and pseudo Q wave (40%); 64% of patients had altered sinus variability on 24-hour Holter monitoring, one patient had a high-grade conduction disorder and another had ventricular tachycardia. On echocardiography, all showed diastolic dysfunction; mean diastolic septum thickness was 13.5mm; only one patient had LVEF impairment but 38% had global longitudinal strain impairment. 10 patients had cardiac MRI, none showed contrast enhancement after gadolinium injection. After median follow-up of 28 months, 4 patients were hospitalized for heart failure, including 2 with cardiogenic shock. Seven (35%) patients died within a median of 10 months from diagnosis. Among patients with Mayo clinic stage 3 (a or b), 67% died within a median of 8 months from the diagnosis. Conclusions To our knowledge, we present the first case series dedicated to the description of cardiac parameters in MIDD patients with cardiac involvement. Except for MRI appearance of cardiac infiltration, these patients showed features close to that of AL amyloid heart disease. Overall prognosis appears seemingly poor in MIDD patients with Mayo Clinic stage 3 cardiac disease. Funding Acknowledgement Type of funding source: None

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Association of maximal stress ergometry performance with troponin T and abdominal aortic calcification score in advanced chronic kidney disease

BMC Nephrology ◽

10.1186/s12882-021-02251-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Roosa Lankinen ◽

Markus Hakamäki ◽

Kaj Metsärinne ◽

Niina Koivuviita ◽

Jussi P. Pärkkä ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Troponin T ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Aortic Calcification ◽

Cardiac Biomarkers ◽

Abdominal Aortic Calcification ◽

Abdominal Aortic ◽

Calcification Score

Abstract Background Cardiac biomarkers Troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (proBNP) and abdominal aortic calcification score (AAC) are associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). The effects of cardiac biomarkers and AAC on maximal exercise capacity in CKD are unknown and were studied. Methods One hundred seventy-four CKD 4–5 patients not on maintenance dialysis underwent maximal bicycle ergometry stress testing, lateral lumbar radiograph to study AAC, echocardiography and biochemical assessments. Results The subjects with proportional maximal ergometry workload (WMAX%) less than 50% of the expected values had higher TnT, proBNP, AAC, left ventricular end-diastolic diameter, left ventricular mass index, E/e’ and pulse pressure, and lower global longitudinal strain compared to the better performing patients. TnT (β = − 0.09, p = 0.02), AAC (β = − 1.67, p < 0.0001) and diabetes (β = − 11.7, p < 0.0001) remained significantly associated with WMAX% in the multivariable model. Maximal ergometry workload (in Watts) was similarly associated with TnT and AAC in addition to age, male gender, hemoglobin and diastolic blood pressure in a respective multivariate model. AAC and TnT showed fair predictive power for WMAX% less than 50% of the expected value with AUCs of 0.70 and 0.75, respectively. Conclusions TnT and AAC are independently associated with maximal ergometry stress test workload in patients with advanced CKD. Trial registration http://www.ClinicalTrials.gov NCT04223726.

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A Novel Prognostic Staging System for Light Chain Amyloidosis (AL) Incorporating Markers of Plasma Cell Burden and Organ Involvement.

Blood ◽

10.1182/blood.v114.22.2797.2797 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2797-2797 ◽

Cited By ~ 3

Author(s):

Shaji Kumar ◽

Angela Dispenzieri ◽

Martha Q. Lacy ◽

Suzzane Hayman ◽

Francis Buadi ◽

...

Keyword(s):

Risk Stratification ◽

Plasma Cell ◽

Light Chain ◽

Cardiac Involvement ◽

Troponin T ◽

Prognostic Score ◽

Staging System ◽

Cardiac Biomarkers ◽

Al Amyloidosis ◽

The Impact

Abstract Abstract 2797 Poster Board II-773 Background: Primary systemic amyloidosis (AL) is characterized by deposition of light chain derived amyloid fibrils in multiple organs leading to varying degree of dysfunction. Cardiac involvement is a common feature of AL, and when significant is highly predictive of poor outcome. The currently used prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro B-type Natriuretic peptide (NT-ProBNP) and is effective at predicting outcome in patients with AL. However, this is driven primarily by the degree of cardiac involvement and does not take into account the degree of plasma cell burden and its impact on the disease course. It is possible that some of the heterogeneity in outcome can be explained by the plasma cell characteristics rather than the degree of the end organ damage. Methods: We examined the baseline clinical and laboratory data from 2119 patients with AL who were seen at our institution with in 90 days of their diagnosis. The data were collected from a prospectively maintained data base, and additional testing was done for free light chain levels (FLC) on stored sera from patients seen before the routine introduction of FLC testing. Cox proportional hazards analysis was performed to estimate the prognostic values of different variables. Results: We first examined the impact of plasma cell clone related characteristics namely, difference between involved and uninvolved FLC (FLC-Diff), bone marrow plasma cell (BMPC) %, plasma cell labeling index (PCLI), beta 2 microglobulin (B2M), and presence of circulating plasma cells, on overall survival (OS) from diagnosis. All variables were dichotomized into high and low based on their median value (FLC-diff: 20 mg/dL, BMPC: 10%, PCLI as a continuous variable, B2M: 3 mg/dL and circulating cells: absent or present). While all were found to be prognostic for OS in univariate analysis; in a multivariate analysis incorporating a stepwise selection only B2M and FLC-diff were significant. We then used these two variables along with the cTnT and NT-ProBNP that are used in the current model to develop a staging system. The median values for all four variables were used for developing the scores. Patients were assigned a score of 1 for presence of each characteristic (FLC difference > 20 mg/dL, troponin-T > 0.02, NT-ProBNP > 1000, and B2M > 3) or 0 if the value was at or below the cutoff. The scores were added to obtain a composite prognostic score that grouped the 370 patients (who had all the variables available for analysis) into 5 groups with very different OS (4.4, 9.3, 24.4, 43, and not reached for stages 4, 3, 2, 1, and 0 respectively; Figure A). However, since the NT-ProBNP did not have independent impact on survival in a multivariable model incorporating all the four variables, we also examined a system that only included FLC-diff, cTnT and B2M. This system again allowed grouping of patients (n=450 with all three variables available) into four distinct groups with divergent outcome with OS of 4.6, 10.5, 36.8, and not reached for stages 3, 2, 1, and 0 respectively; (Figure B). Conclusion: Incorporation of plasma cell related measurements into the existing staging system using cardiac biomarkers allows better risk stratification of patients with AL amyloidosis. The system using FLC, B2M and troponin has the advantage of easily available laboratory values and can be widely adopted. Addition of NT-ProBNP into the system allows better refinement of the intermediate risk groups. This system will allow upfront risk stratification and development of risk-adapted therapies for patients with AL. Disclosures: Gertz: Genzyme: Research Funding.

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Quality of Life Is Associated with Cardiac Biomarkers, Echocardiographic Indices, and Mortality in CKD Stage 4–5 Patients Not on Dialysis

Blood Purification ◽

10.1159/000510984 ◽

2020 ◽

pp. 1-8

Author(s):

Markus Hakamäki ◽

Roosa Lankinen ◽

Tapio Hellman ◽

Niina Koivuviita ◽

Jussi P. Pärkkä ◽

...

Keyword(s):

Quality Of Life ◽

Kidney Disease ◽

Troponin T ◽

Short Form ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

Stage 4 ◽

Ckd Stage

Introduction: Patients with CKD have an impaired health-related quality of life (QoL). Most studies have been conducted on dialysis patients, and less is known about QoL and its determinants in predialysis patients. We studied the association between QoL and comorbidities, cardiac biomarkers, echocardiography, and mortality in patients with CKD stage 4–5 not on dialysis. Methods: A total of 140 patients enrolled in the Chronic Arterial Disease, Quality of Life and Mortality in Chronic Kidney Injury (CADKID) study filled the Kidney Disease Quality of Life Short Form (KDQOL-SF) at the beginning of the study. Echocardiography and biochemical parameters were obtained at baseline. Patients were followed up for at least 2 years or until death. Results: The median age was 66 years, and 51 (36%) patients were female. The median estimated glomerular filtration rate was 13 mL/min per 1.73 m2. Obesity, diabetes, atrial fibrillation, and congestive heart failure were associated with lower QoL scores in multiple KDQOL-SF domains. Cardiac biomarkers, troponin T (p = 0.02), N-terminal pro-B-type natriuretic peptide (p = 0.006), and the echocardiographic parameter of cardiac systolic function left ventricular global longitudinal strain (p = 0.02) were significant predictors of lower physical component summary (PCS) score in multivariable regression models after controlling for age, BMI, and diabetes. A low PCS score predicted mortality in a multivariable Cox proportional hazards model [HR 0.96 (95% CI 0.92–0.99), p = 0.03]. QoL was not associated with kidney disease progression. Conclusion: Impaired QoL in CKD stage 4–5 patients not on dialysis is associated with cardiac biomarker levels, echocardiographic indices, and mortality.

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Can myocardial work indices contribute to the exploration of patients with cardiac amyloidosis?

Open Heart ◽

10.1136/openhrt-2020-001346 ◽

2020 ◽

Vol 7 (2) ◽

pp. e001346

Author(s):

Aénora Roger-Rollé ◽

Eve Cariou ◽

Khailène Rguez ◽

Pauline Fournier ◽

Yoan Lavie-Badie ◽

...

Keyword(s):

Cardiac Amyloidosis ◽

Characteristic Curve ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Peak Oxygen Consumption ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Echocardiographic Parameters ◽

Global Work ◽

Better Than

BackgroundCardiac amyloidosis (CA) is a life-threatening restrictive cardiomyopathy. Identifying patients with a poor prognosis is essential to ensure appropriate care. The aim of this study was to compare myocardial work (MW) indices with standard echocardiographic parameters in predicting mortality among patients with CA.MethodsClinical, biological and transthoracic echocardiographic parameters were retrospectively compared among 118 patients with CA. Global work index (GWI) was calculated as the area of left ventricular pressure–strain loop. Global work efficiency (GWE) was defined as percentage ratio of constructive work to sum of constructive and wasted works. Sixty-one (52%) patients performed a cardiopulmonary exercise.ResultsGWI, GWE, global longitudinal strain (GLS), left ventricular ejection fraction (LVEF) and myocardial contraction fraction (MCF) were correlated with N-terminal prohormone brain natriuretic peptide (R=−0.518, R=−0.383, R=−0.553, R=−0.382 and R=−0.336, respectively; p<0.001). GWI and GLS were correlated with peak oxygen consumption (R=0.359 and R=0.313, respectively; p<0.05). Twenty-eight (24%) patients died during a median follow-up of 11 (4–19) months. The best cut-off values to predict all-cause mortality for GWI, GWE, GLS, LVEF and MCF were 937 mm Hg/%, 89%, 10%, 52% and 15%, respectively. The area under the receiver operator characteristic curve of GWE, GLS, GWI, LVEF and MCF were 0.689, 0.631, 0.626, 0.511 and 0.504, respectively.ConclusionIn CA population, MW indices are well correlated with known prognosis markers and are better than LVEF and MCF in predicting mortality. However, MW does not perform better than GLS.

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Development and validation of a survival staging system incorporating BNP in patients with light chain amyloidosis

Blood ◽

10.1182/blood-2018-06-858951 ◽

2019 ◽

Vol 133 (3) ◽

pp. 215-223 ◽

Cited By ~ 36

Author(s):

Brian Lilleness ◽

Frederick L. Ruberg ◽

Roberta Mussinelli ◽

Gheorghe Doros ◽

Vaishali Sanchorawala

Keyword(s):

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Light Chain ◽

Cardiac Involvement ◽

Staging System ◽

Stage I ◽

Stage Iiib ◽

Stage Ii ◽

Al Amyloidosis ◽

Derivation Cohort

Abstract Immunoglobulin light chain amyloidosis (AL amyloidosis) is caused by misfolded light chains that form soluble toxic aggregates that deposit in tissues and organs, leading to organ dysfunction. The leading determinant of survival is cardiac involvement. Current staging systems use N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins T and I (TnT and TnI) for prognostication, but many centers do not offer NT-proBNP. We sought to derive a new staging system using brain natriuretic peptide (BNP) that would correlate with the Mayo 2004 staging system and be predictive for survival in AL amyloidosis. Two cohorts of patients were created: a derivation cohort of 249 consecutive patients who had BNP, NT-proBNP, and TnI drawn simultaneously to create the staging system and a complementary cohort of 592 patients with 10 years of follow-up to determine survival. In the derivation cohort, we found that a BNP threshold of more than 81 pg/mL best associated with Mayo 2004 stage and also best identified cardiac involvement. Three stages were developed based on a BNP higher than 81 pg/mL and a TnI higher than 0.1 ng/mL and compared with Mayo 2004 with high concordance (κ = 0.854). In the complementary cohort, 25% of patients had stage I, 44% had stage II, 15% had stage III, and 16% had stage IIIb disease with a median survival not reached in stage I, 9.4 years in stage II, 4.3 years in stage III, and 1 year in stage IIIb. This new Boston University biomarker scoring system will allow centers without access to NT-proBNP the ability to appropriately stage patients with AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00898235.

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Hereditary transthyretin amyloidosis: predictors of conduction disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.2111 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A.F Dias De Frias ◽

P Rodrigues ◽

M Trepa ◽

M Fontes-Oliveira ◽

R Costa ◽

...

Keyword(s):

Troponin T ◽

Pacemaker Implantation ◽

Outcome Data ◽

Left Ventricular ◽

Cardiac Biomarkers ◽

P Value ◽

Neurologic Manifestations ◽

Ventricular Pacing ◽

Transthyretin Amyloidosis ◽

Formal Indication

Abstract Introduction Pacemakers are frequently needed due to a high prevalence of conduction disease in mutated ATTR amyloidosis (mATTR). We aimed to identify the variables associated with the need of pacemaker implantation in this population. Methods We retrospectively studied 255 patients with suspicion of heart involvement of mATTR observed at our cardiology clinic during the last year. Clinical and outcome data were retrieved by chart review. We have defined the need for pacemaker implantation as: 1) the formal guidelines indications or 2) Ventricular pacing >10% in patients who had prophylactic pacemaker implantation prior to liver transplantation (LT). This way, we have defined 3 different groups: group 1: patients with no evidence of conduction disease; group 2: patients with conduction disease, but no formal indication for pacemaker implantation; and group 3: patients with formal indication for pacemaker implantation or ventricular pacing >10% in patients who had prophylactic pacemaker implantation prior to hepatic transplantation. Results We included 255 patients (50±14 years, 53% male, 52.5% treated with tafamidis and 27% had prior LT, and 10% with atrial fibrillation), 43.3% with no evidence of conduction disease, 32.3% with conduction disease, but no formal indication for pacemaker implantation and 24.4% with formal indication for pacemaker implantation. Patients with formal indication for pacemaker implantation were older, with longer duration of neurologic manifestations, with higher concentration of both Troponin T and NT-proBNP and with higher number of organs affected. In multivariate analysis, longer duration of neurologic manifestations (OR 1.090 – 95% IC: 1.036–1.145, p-value 0.001), Left ventricular (LV) maximal wall thickness (OR 1.230 – 95% CI: 1.070–1.414, p-value 0.004), neurologic staging (OR 3.420 – 95% CI: 1.443–8.104, p-value 0.005) and higher number of organs affected (OR 1.719 – 95% CI: 1.218–2.424, p-value 0.002) all showed to be independent predictors of the need for pacemaker implantation, in contrast to LV ejection fraction and serum concentration of Troponin T and NT-proBNP. We've also found a statistical significant association between conduction disease and ophthalmic manifestations. Conclusions Our findings suggest that the need for pacemaker implantation in patients with mATTR is closer linked to the duration, severity and affected number of organs than to cardiac biomarkers or echocardiographic findings. Funding Acknowledgement Type of funding source: None

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