Clinical and prognostic implications of capillary density in patients with cardiac light chain amyloidosis

Abstract

Aims Cardiac involvement is crucial factor determining outcomes of light chain (AL) amyloidosis. This study evaluated whether capillary density (CD) quantified from endomyocardial biopsy is associated with structural and functional parameters of amyloid heart. Also, we investigated whether capillary density improves the prognostic value of the current staging system in AL amyloidosis patients with cardiac involvement. Methods and results A total of 67 patients with biopsy‐proven AL cardiac amyloidosis were prospectively enrolled in this study. All patients underwent transthoracic echocardiography and EBM at the time of diagnosis. Left ventricle global longitudinal strain was evaluated on two‐dimensional strain echocardiography. The primary endpoint was all‐cause mortality. Amyloid load and capillary density were calculated on endomyocardial biopsy stained immunohistochemically with antibody against amyloid P and CD31, respectively. Among the study population, 37 patients (55.2%) were classified as Stage IV, and the cumulative incidence of death at 1 year was 34% (23 patients). A total of 65 (97%) patients underwent chemotherapy. CD showed a significant correlation with left ventricle global longitudinal strain (r = 0.274, P = 0.025), log N‐terminal pro‐B type natriuretic peptide (r = −0.311, P = 0.005), and amyloid load (r = −0.438, P < 0.001). Patients with a CD ≤ 220/mm2 were at significantly higher risk of death than those with a CD > 220/mm2 (P = 0.026 by log‐rank test). A model based on the 2012 Mayo staging system and CD showed significantly better discrimination and reclassification ability than a model using the 2012 Mayo staging system alone (C‐index 0.582 vs.0.689, P for difference <0.001). Conclusions Capillary density was significantly related to the severity of amyloid deposits in the myocardium and showed incremental prognostic value in addition to the 2012 Mayo staging system.

Capillaries as a Therapeutic Target for Heart Failure

“…In symptomatic patients with AL or transthyretin amyloidosis, myocyte blood flow became lower than in hypertensive patients exhibiting LV hypertrophy 57) . Recently, Kim et al showed direct evidence of reduced capillary density in AL amyloidosis patients 58) . They analyzed cardiac biopsy samples and showed capillary density had a negative correlation with NT-proBNP level, amyloid load, LV diastolic, and systolic function 58) .…”

“…Recently, Kim et al showed direct evidence of reduced capillary density in AL amyloidosis patients 58) . They analyzed cardiac biopsy samples and showed capillary density had a negative correlation with NT-proBNP level, amyloid load, LV diastolic, and systolic function 58) . In this paper, the patients exhibiting capillary density of ＞220/mm 2 were shown to have a better prognosis than those exhibiting ＜220/mm 2, 58) .…”

“…They analyzed cardiac biopsy samples and showed capillary density had a negative correlation with NT-proBNP level, amyloid load, LV diastolic, and systolic function 58) . In this paper, the patients exhibiting capillary density of ＞220/mm 2 were shown to have a better prognosis than those exhibiting ＜220/mm 2, 58) . Together with therapy targeting removal of amyloid deposition, whether maintaining capillarization becomes a therapy for amyloidosis remains an open question to be explored.…”

Evaluation of contemporary echocardiographic and histomorphology parameters in predicting mortality in patients with endomyocardial biopsy-proven cardiac AL amyloidosis

“…The investigators of this study also quantified capillary density on the EMB samples as the number of capillaries, which were counted after they were stained with a specific antibody against endothelium (CD31), divided by area (mm 2 ). The authors reported that lower capillary density correlated with amyloid load and predicted mortality among 67 patients with biopsy-proven AL cardiac amyloidosis ( 12 ). When added to the 2012 Mayo staging system, capillary density led to better discrimination and reclassification ability compared to the 2012 Mayo staging system alone ( 12 ).…”

“…In some recent reports, the prognostic value of these systems has been augmented with echo-derived strain patterns, such as left ventricular (LV) global longitudinal strain (GLS) and the apical to basal longitudinal strain gradient ( 11 ). Furthermore, the capillary density within the myocardium on histopathology has also been shown to improve the prognostic value of the 2012 Mayo staging system ( 12 ).…”