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Elasticity because of fibrosis comprehensively might consequently result in observed regional myocardial deformation abnormalities in these patients. Moreover, locally increased turbulent flow in the left ventricular outflow tract near the basal segment might also aggravate apoptosis [27] and subsequent fibrosis and thus contribute to reduced contractility at basal segments in these KN-93 (phosphate) web patients with CA. In fact, the observed reduction in longitudinal strain in the basal and mid segments with a preserved strain in apical segments was also observed in patients with decompensated hypertrophic cardiomyopathy [28], future studies are warranted to explore if the observed “baso-apical” strain gradient is a special “pathognomonic feature” or not for patients with cardiac amyloidosis.Prognostic ImplicationPrevious studies have demonstrated that LV hypertrophy identifies a population at high 23727046 risk for cardiovascular disease and predicts an increased risk of cardiovascular morbidity and death independent of age, blood pressure, cigarette use, diabetes, obesity [29,30]. It has also been suggested that LV hypertrophy and reduced EF are associated with poor outcome in AL cardiac MedChemExpress KPT-9274 amyloidosis patients [3,31]. The current study shows combining conventional echocardiographic parameters with the STI derived base-to-apex intra-wall longitudinal deformation gradient is helpful for staging the patients with CA, and deformation changes is superior to hypertrophy and EF on predicting the prognosis in patients with CA.Table 7. Cox proportional-hazards regression analysis of clinical and echocardiographic predictors on mortality.Wald Univariate analysis Age Gender NYHA class.2 LV mean thickness 14 mm Ejection fraction,50 Mid-septum LSsys,11 Multivariate analysis NYHA class Mid-septum LSsys ( ) 3.995 6.516 0.156 0.553 2.508 0.003 0.844 5.Hazard ratio95 CIP value1.01 1.50 2.77 1.03 1.80 4.0.97 ?1.05 0.52 ?4.32 0.79 ?9.78 0.31 ?3.49 0.52 ?6.26 1.31 ?17.0.693 0.457 0.113 0.959 0.358 0.3.21 4.1.02 ?10.06 1.42 ?14.0.046 0.CI: confidence interval; NYHA: New York Heart Association; LV: left ventricular; LSsys: longitudinal systolic strain. doi:10.1371/journal.pone.0056923.tMyocardial Strain in Systemic Amyloidosis PatientsTable 8. Cox proportional-hazards regression analysis of AL amyloidosis related predictors on mortality.Wald Univariate analysis Age Gender Light chain type Number of involvement organs Hematological response to treatment High-dose melphalan plus ASCT Oral melphalan or plus prednisone or bortezomib Multivariate analysis High-dose melphalan plus ASCT Oral melphalan or plus prednisone or bortezomib Number of involvement organs CI: confidence interval; ASCT: autologous stem-cell transplantation. doi:10.1371/journal.pone.0056923.t008 5.118 8.082 8.854 0.050 0.356 0.151 8.714 0.035 5.182 6.Hazard ratio95 CIP value0.99 0.83 1.26 4.07 0.88 6.58 13.0.91?.07 0.45?.53 0.39?.06 1.60?0.33 0.23?.40 1.30?3.35 1.86?4.0.823 0.551 0.698 0.003 0.851 0.023 0.6.35 11.22 3.1.28?1.48 2.12?9.42 1.54?.0.024 0.004 0.Study LimitationsThe patient cohort is relatively small in the present study. Studies with larger patient number are warranted to overcome this limitation and verify the outcome results. The prognostic potential of NT-proBNP and troponin in patients with AL amyloidosis is widely accepted. However, NT-proBNP and troponin were available in only 23 patients in our cohort. It is therefore very difficult to determine the prognostic value of these cardiac biomarkers due.Elasticity because of fibrosis comprehensively might consequently result in observed regional myocardial deformation abnormalities in these patients. Moreover, locally increased turbulent flow in the left ventricular outflow tract near the basal segment might also aggravate apoptosis [27] and subsequent fibrosis and thus contribute to reduced contractility at basal segments in these patients with CA. In fact, the observed reduction in longitudinal strain in the basal and mid segments with a preserved strain in apical segments was also observed in patients with decompensated hypertrophic cardiomyopathy [28], future studies are warranted to explore if the observed “baso-apical” strain gradient is a special “pathognomonic feature” or not for patients with cardiac amyloidosis.Prognostic ImplicationPrevious studies have demonstrated that LV hypertrophy identifies a population at high 23727046 risk for cardiovascular disease and predicts an increased risk of cardiovascular morbidity and death independent of age, blood pressure, cigarette use, diabetes, obesity [29,30]. It has also been suggested that LV hypertrophy and reduced EF are associated with poor outcome in AL cardiac amyloidosis patients [3,31]. The current study shows combining conventional echocardiographic parameters with the STI derived base-to-apex intra-wall longitudinal deformation gradient is helpful for staging the patients with CA, and deformation changes is superior to hypertrophy and EF on predicting the prognosis in patients with CA.Table 7. Cox proportional-hazards regression analysis of clinical and echocardiographic predictors on mortality.Wald Univariate analysis Age Gender NYHA class.2 LV mean thickness 14 mm Ejection fraction,50 Mid-septum LSsys,11 Multivariate analysis NYHA class Mid-septum LSsys ( ) 3.995 6.516 0.156 0.553 2.508 0.003 0.844 5.Hazard ratio95 CIP value1.01 1.50 2.77 1.03 1.80 4.0.97 ?1.05 0.52 ?4.32 0.79 ?9.78 0.31 ?3.49 0.52 ?6.26 1.31 ?17.0.693 0.457 0.113 0.959 0.358 0.3.21 4.1.02 ?10.06 1.42 ?14.0.046 0.CI: confidence interval; NYHA: New York Heart Association; LV: left ventricular; LSsys: longitudinal systolic strain. doi:10.1371/journal.pone.0056923.tMyocardial Strain in Systemic Amyloidosis PatientsTable 8. Cox proportional-hazards regression analysis of AL amyloidosis related predictors on mortality.Wald Univariate analysis Age Gender Light chain type Number of involvement organs Hematological response to treatment High-dose melphalan plus ASCT Oral melphalan or plus prednisone or bortezomib Multivariate analysis High-dose melphalan plus ASCT Oral melphalan or plus prednisone or bortezomib Number of involvement organs CI: confidence interval; ASCT: autologous stem-cell transplantation. doi:10.1371/journal.pone.0056923.t008 5.118 8.082 8.854 0.050 0.356 0.151 8.714 0.035 5.182 6.Hazard ratio95 CIP value0.99 0.83 1.26 4.07 0.88 6.58 13.0.91?.07 0.45?.53 0.39?.06 1.60?0.33 0.23?.40 1.30?3.35 1.86?4.0.823 0.551 0.698 0.003 0.851 0.023 0.6.35 11.22 3.1.28?1.48 2.12?9.42 1.54?.0.024 0.004 0.Study LimitationsThe patient cohort is relatively small in the present study. Studies with larger patient number are warranted to overcome this limitation and verify the outcome results. The prognostic potential of NT-proBNP and troponin in patients with AL amyloidosis is widely accepted. However, NT-proBNP and troponin were available in only 23 patients in our cohort. It is therefore very difficult to determine the prognostic value of these cardiac biomarkers due.

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