Performance analysis of AL amyloidosis cardiac biomarker staging systems with special focus on renal failure and atrial arrhythmia.

Systemic light chain amyloidosis is a rare and life-threatening disorder, for which accurate risk stratification is crucial. Current cardiac staging systems (MAYO2004, MAYO3b, and MAYO2012) are mainly based on biomarkers, which have uncertain reliability in the context of atrial fibrillation, arrhythmia or pacemaker stimulation as well as renal insufficiency. We compared the performance of the established staging systems with particular regard to these comorbidities in 1,224 patients with systemic light chain amyloidosis diagnosed at our center from July 2002 until March 2017. We first characterized the subsets with an estimated glomerular filtration rate <50 mL/min/1.73 m2 (415 patients) and any kind of atrial arrhythmia (183 patients) as unique high-risk subgroups with similarly increased cardiac biomarkers (χ2-test, all P<0.001). This resulted in a shift towards higher risk stages and reduced median overall survival compared to those of patients with better kidney function or without atrial arrhythmia in univariate analyses (13 vs 46 months and 17 vs 53 months, respectively; both P<0.001). Performance analysis revealed that predictions in the entire cohort were least precise with the MAYO2004 staging system and most precise with the MAYO3b system. This performance pattern was almost preserved for patients with an estimated glomerular filtration rate <50 mL/min/1.73 m2, but less so for those with atrial arrhythmias. The MAYO3b staging system was most robust. Importantly, atrial arrhythmia retained its prognostic value in multivariable analysis including age, difference between involved and uninvolved free light chains, and any staging system, while estimated glomerular filtration rate <50 mL/min/1.73 m2 was not statistically significant in multivariable analysis with the MAYO3b staging system. In conclusion, our results favor the MAYO3b staging system due to its consistently best performance and retained applicability in the subgroups with atrial arrhythmia and estimated glomerular filtration rate <50 mL/min/1.73 m2.

Prognostic value of novel imaging parameters derived from standard cardiovascular magnetic resonance in high risk patients with systemic light chain amyloidosis.

BACKGROUND: The differentiated assessment of functional parameters besides morphological changes is essential for the evaluation of prognosis in systemic immunoglobulin light chain (AL) amyloidosis. METHODS: Seventy-four subjects with AL amyloidosis and presence of late gadolinium enhancement (LGE) pattern typical for cardiac amyloidosis were analyzed. Long axis strain (LAS) and myocardial contraction fraction (MCF), as well as morphological and functional markers, were measured. The primary endpoint was death, while death and heart transplantation served as a composite secondary endpoint. RESULTS: After a median follow-up of 41 months, 29 out of 74 patients died and 10 received a heart transplant. Left ventricular (LV) functional parameters were reduced in patients, who met the composite endpoint (LV ejection fraction 51% vs. 61%, LAS - 6.9% vs - 10%, GLS - 12% vs - 15% and MCF 42% vs. 69%; p <  0.001 for all). In unadjusted univariate analysis, LAS (HR = 1.05, p <  0.001) and MCF (HR = 0.96, p <  0.001) were associated with reduced transplant-free survival. Kaplan-Meier analyses showed a significantly lower event-free survival in patients with reduced MCF. MCF and LAS performed best to identify high risk patients for secondary endpoint (Log-rank test p <  0.001) in a combined model. Using sequential Cox regression analysis, the addition of LAS and MCF to LV ejection fraction led to a significant increase in the predictive power of the model (χ2 (df = 1) = 28.2, p <  0.001). CONCLUSIONS: LAS and MCF as routinely available and robust CMR-derived parameters predict outcome in LGE positive AL amyloidosis. Patients with impaired LV function in combination with reduced LAS and MCF are at the highest risk for death and heart transplantation.

Regional differences in prognostic value of cardiac valve plane displacement in systemic light-chain amyloidosis.

BACKGROUND: To compare the prognostic value of cardiac valve plane displacement (CVPD) on various locations in cardiac light chain (AL) amyloidosis. METHODS: Consecutive patients with biopsy-proven cardiac involvement in AL amyloidosis who had undergone cardiovascular magnetic resonance (CMR) between 2005 and 2014 in our institution, were retrospectively identified and data analyzed. The primary combined endpoint was all-cause mortality or heart transplantation. Systolic CVPD were obtained from standard cine bSSFP in 2-, 3- and 4-chamber views at anterior aortic plane systolic excursion (AAPSE); anterior, anterolateral, inferolateral, inferior, inferoseptal mitral (MAPSE); and lateral tricuspid (TAPSE) annular segments. RESULTS: We identified 68 patients (58 ± 10 years; 59% male). Median follow-up period was 1.2 years (IQR, 0.3-4.1). Significant differences in CVPD between patients who reached a primary endpoint (n = 44) and transplant-free survivors were found only for AAPSE (6.1 mm (IQR, 4.6-9.4) vs. 8.8 mm (IQR, 6.9-10.4); p = 0.02) and MAPSEanterolateral (7.3 mm (IQR, 5.4-11.7) vs. 10.5 mm (IQR, 8.1-13.4); p = 0.03). AAPSE (χ2 = 15.6; p = 0.0002) provided the best predictive value for transplant-free survival compared to all other valvular plane locations. A high-risk cutoff (AAPSE ≤ 7.6 mm) was calculated by ROC analysis to predict all-cause death or heart transplantation within 6 months from index examination (AUC = 0.80; CI: 0.68 to 0.89; p < 0.0001). AAPSE added incremental prognostic power to an imaging prediction model of late gadolinium enhancement and global longitudinal strain (GLS) (∆χ2 = 5.8, p = 0.02) as well as to a clinical model including Karnofsky index and NT-proBNP (∆χ2 = 6.2, p = 0.01). CONCLUSION: In patients with cardiac involvement in AL amyloidosis, systolic CVPD obtained from standard long axis cine views appear to indicate outcome better, when obtained in the anterior aortic plane (AAPSE) and provide incremental prognostic value to LGE and strain measurements.

Limits of the possible: diagnostic image quality in coronary angiography with third-generation dual-source CT.

BACKGROUND: The usage of coronary CT angiography (CTA) is appropriate in patients with acute or chronic chest pain; however the diagnostic accuracy may be challenged with increased Agatston score (AS), increased heart rate, arrhythmia and severe obesity. Thus, we aim to determine the potential of the recently introduced third-generation dual-source CT (DSCT) for CTA in a 'real-life' clinical setting. METHODS: Two hundred and sixty-eight consecutive patients (age: 67 ± 10 years; BMI: 27 ± 5 kg/m²; 61% male) undergoing clinically indicated CTA with DSCT were included in the retrospective single-center analysis. A contrast-enhanced volume dataset was acquired in sequential (SSM) (n = 151) or helical scan mode (HSM) (n = 117). Coronary segments were classified in diagnostic or non-diagnostic image quality. A subset underwent invasive angiography to determine the diagnostic accuracy of CTA. RESULTS: SSM (96.8 ± 6%) and HSM (97.5 ± 8%) provided no significant differences in the overall diagnostic image quality. However, AS had significant influence on diagnostic image quality exclusively in SSM (B = 0.003; p = 0.0001), but not in HSM. Diagnostic image quality significantly decreased in SSM in patients with AS ≥2,000 (p = 0.03). SSM (sensitivity: 93.9%; specificity: 96.7%; PPV: 88.6%; NPV: 98.3%) and HSM (sensitivity: 97.4%; specificity: 94.3%; PPV: 86.0%; NPV: 99.0%) provided comparable diagnostic accuracy (p = n.s.). SSM yielded significantly lower radiation doses as compared to HSM (2.1 ± 2.0 vs. 5.1 ± 3.3 mSv; p = 0.0001) in age and BMI-matched cohorts. CONCLUSION: SSM in third-generation DSCT enables significant dose savings and provides robust diagnostic image quality in patients with AS ≤2000 independent of heart rate, heart rhythm or obesity.