Impaired exercise capacity and left ventricular function in long-term adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late cardiotoxic effects of cancer treatment, but conflicting evidence exists on the effects of anthracyclines on left ventricular (LV) diastolic function and exercise capacity. PROCEDURE: We performed a cross-sectional study with comprehensive echocardiography in 138 adult survivors of childhood ALL, median 23.4 years after diagnosis. Pulsed tissue Doppler measurements of early diastolic mitral annular velocities (e') were used for the assessment of diastolic function, and compared to 138 matched controls. Of the survivors, 133 also performed ergospirometry measuring peak oxygen uptake (VO2 max). Associations between cancer treatment, LV function, and VO2 max were analyzed. RESULTS: The survivor group had lower e' values than controls (e' septal 11.0 vs. 12.6 cm/s, P < 0.001), but the difference was confined to the subgroup of anthracycline treated survivors (median cumulative dose 120 mg/m(2) ). Anthracycline exposure was inversely correlated with e' (regression coefficient -1.581, P=0.009). Reduced VO2 max/kg occurred in 47% of the survivors, but more often in anthracycline treated survivors (56%) than anthracycline naïve survivors (17%, P<0.001). Anthracycline exposure was inversely correlated with VO2 max/kg (regression coefficient -3.084, P = 0.05 in multivariate analysis). Furthermore, associations were observed between measures of LV function and VO2 max/kg, and e' was the best predictor of VO2 max/kg (standardized coefficient 0.355, P < 0.001 in multivariate analysis). CONCLUSIONS: Adult survivors of childhood ALL have increased risk for impaired LV diastolic function and impaired exercise capacity, both associated with previous anthracycline exposure. Furthermore, there is an association between LV diastolic function and exercise capacity.

Prevalence of transthyretin amyloid cardiomyopathy in pacemaker patients.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by increased wall thickness, diastolic dysfunction and progressive heart failure symptoms. The disease may infiltrate the conduction system leading to conduction disturbances requiring an implantation of permanent cardiac pacemaker (PM), but the extent is unknown. Here, we report the prevalence of ATTR-CM in patients ≥65 years with PM. METHODS AND RESULTS: In this prospective, cross-sectional single-centre study patients were recruited from our out-patient pacemaker clinic. Eligibility criteria were age above 65 years, permanent cardiac pacemaker and competent to give informed consent. Patients underwent echocardiography at the pacemaker visit and were referred to 99mTc-DPD-scintigraphy (DPD) and blood samples if septum thickness was ≥12 mm, defined as left ventricular hypertrophy (LVH). Fifty eight of the 128 patients had LVH on echocardiography. Eleven patients had a DPD-scintigraphy based diagnosis of ATTR-CM, which represent 19% of patients with LVH and 9% of the total cohort. Patients diagnosed with ATTR-CM had higher concentrations of cardiac biomarkers (P < 0.001), higher E/E' (P = 0.001), and lower global longitudinal strain (P = 0.003) on echocardiography and more heart failure symptoms (P = 0.001). CONCLUSIONS: The prevalence of ATTR-CM in elderly patients with PM and LVH on echocardiography was 19%.

Utility of Global Longitudinal Strain by Echocardiography to Detect Left Ventricular Dysfunction in Long-Term Adult Survivors of Childhood Lymphoma and Acute Lymphoblastic Leukemia.

Measuring left ventricular (LV) global longitudinal strain (GLS) is recommended in screening of long-term cancer survivors for cardiotoxicity. However, there are limited data on GLS in this setting, in particular in survivors with apparently normal LV function without risk factors of impaired GLS. In the present study, we measured GLS in 191 adult survivors of childhood lymphoma or acute lymphoblastic leukemia, with normal LV ejection fraction and fractional shortening (FS) and without known hypertension, diabetes mellitus, myocardial infarction, or stroke. We compared GLS in the survivors with 180 controls. Mean GLS was -19.0 ± 2.2% in the survivor group and -21.4 ± 2.0% in the controls (p <0.001). Impaired GLS, defined as mean - 1.96 SDs in the control group, occurred in 53 of 191 survivors (28%). We included survivors with impaired LV ejection fraction and/or FS or traditional risk factors (n = 231 in all) in multiple regression analyses to explore associations with previous cancer treatment. Survivors treated with mediastinal radiotherapy had an odds ratio of impaired GLS of 5.2 (95% confidence interval 2.2 to 12) compared with other survivors. Survivors treated with cumulative anthracycline doses >300 mg/m(2) had an odds ratio of 4.8 (95% confidence interval 1.7 to 14) of impaired GLS. In conclusion, this study demonstrates a high proportion of LV dysfunction assessed by GLS in apparently healthy adult survivors of childhood cancer. Impaired GLS was associated with previous exposure to mediastinal radiotherapy and high doses of anthracyclines. The prognostic role of measuring GLS in this specific patient population should be examined in prospective studies.

Right ventricular function in long-term adult survivors of childhood lymphoma and acute lymphoblastic leukaemia.

AIMS: Little is known about right ventricular (RV) function in survivors of childhood cancer, although both anthracyclines and radiotherapy represent potentially cardiotoxic treatment. We hypothesized that adult survivors of childhood malignant lymphoma or acute lymphoblastic leukaemia would have impaired RV function. METHODS AND RESULTS: We examined RV dimensions and function by echocardiography in 246 survivors, mean 21.7 years after diagnosis, and in 211 matched controls. Of the survivors, 84% had been exposed to anthracyclines, mediastinal radiotherapy, or both. Compared with controls, all mean measures of RV function were lower in the survivor group: fractional area change (44.5 vs. 48.6%, P < 0.001), tricuspid annular plane systolic excursion (2.24 vs. 2.49 cm, P < 0.001), peak systolic tricuspid annular velocity (12.1 vs. 13.0 cm/s, P < 0.001), and free wall strain (-26.5 vs. -28.4%, P < 0.001). In contrast, there were little differences in RV diastolic dimensions. Lower measures of RV function were found in all survivor subgroups having received cardiotoxic treatment, but not in the 16% of survivors unexposed to anthracyclines or mediastinal radiotherapy. Signs of RV systolic dysfunction were found in 30% of the survivors, and more than 3 times more often in survivors with left ventricular dysfunction. CONCLUSION: Long-term survivors of childhood lymphoma or acute lymphoblastic leukaemia frequently have impaired RV function compared with controls. As this is associated with increased risk of heart failure and death in many other conditions, we recommend increased attention to RV function in childhood survivors. Whether RV dysfunction impairs prognosis in this patient group should be examined in longitudinal studies.

Left ventricular function in long-term survivors of childhood lymphoma.

Survivors of childhood lymphoma (CL) have markedly increased risk of developing heart failure. Echocardiographic studies after cardiotoxic treatment have primarily demonstrated left ventricular (LV) systolic dysfunction. In the present study, we hypothesized that longer follow-up and a more comprehensive echocardiographic examination would reveal more cardiac abnormalities. We conducted a cross-sectional study with echocardiography 20.4 ± 8.6 years after diagnosis in 125 survivors of CL, grouped according to treatment methods, and compared with matched controls. Treatment included mediastinal radiotherapy (median 40.0 Gy) in 66 and anthracyclines (median dose 160 mg/m(2)) in 92 survivors of CL. Abnormal LV function, left-sided valve dysfunction, or both occurred in 62 patients (50%). Diastolic dysfunction occurred in 29%. Compared with control subjects, mitral annular early diastolic velocities (e') were reduced in patients (septal e' 0.09 ± 0.03 vs 0.12 ± 0.03 m/s, p <0.001), and the E/e' ratio was increased, particularly after mediastinal radiotherapy (10.6 ± 6.4 vs 5.6 ± 1.3, p <0.001). Survivors of CL had lower fractional shortening than control subjects (32 ± 6 vs 36 ± 7, p <0.001), but mean ejection fraction was equal and overt systolic dysfunction was infrequent. After mediastinal radiotherapy alone, global longitudinal myocardial strain was lower (p <0.05) compared with other treatment groups. Left-sided valvular dysfunction occurred in 55% of patients after mediastinal radiotherapy. In conclusion, survivors of CL had reduced LV diastolic function assessed by tissue Doppler imaging. This was more pronounced after mediastinal radiotherapy, which also frequently led to valvular disease. Systolic function was normal in most survivors of CL.