Cardiac status in bone tumor survivors up to nearly 19 years after treatment with doxorubicin: a longitudinal study.

BACKGROUND: Longitudinal assessment of cardiac toxicity in anthracycline-treated long-term bone tumor survivors. PROCEDURES: Cardiac status was assessed in 29 patients 14.1 (range 7-18.7) years after treatment with doxorubicin (DOXO) 360 mg/m(2) (median 225-550). The median age of the patients at the time of the study was 32.5 years (range 19.7-52). The evaluation consisted of an electrocardiogram (ECG), 24-hr ambulatory ECG with analysis of heart rate variability (HRV) and echocardiography. The results were compared to those of a study of the same patients that was performed 5 years earlier 8.9 years (range 2.3-14.1) after treatment. [Postma et al.: Med Pediatr Oncol 26:230-237, 1996] RESULTS: We found no progression of ECG abnormalities, arrhythmias, or echocardiographic abnormalities. Females were at risk for reduced contractility (P = 0.006). HRV was significantly reduced compared to age- and sex-matched controls and compared to the previous results. CONCLUSIONS: Anthracycline-related late echocardiographic abnormalities and arrhythmias detected 8.9 years after treatment, showed no further deterioration with ongoing follow-up. However, there was a significant reduction of HRV. This suggests that HRV might be a sensitive test for detection of anthracycline-induced cardiac toxicity.

A large family characterised by nocturnal sudden death.

BACKGROUND: We recently identified a novel mutation in large family characterised by premature nocturnal sudden death. In the present paper we provide an overview of the findings in this family. METHODS: From 1958 onwards, when the first patient presented, we collected clinical data on as many family members as possible. After identification in 1998 of the underlying genetic disorder (SCN5A, 1795insD), genotyping was performed diagnostically. RESULTS: Since 1905 unexplained sudden death occurred in 26 family members, 17 of whom died during the night. Besides sudden death, symptomatology was rather limited; only six patients reported syncopal attacks. In one of them, a 13-year-old boy, asystolic episodes up to nine seconds were documented. Until now, the mutation has been found in 114 family members (57 males, 57 females). Carriers of the mutant gene exhibited bradycardia-dependent QT-prolongation, intrinsic sinus node dysfunction, generalised conduction abnormalities, a paucity of ventricular ectopy, and the Brugada sign. Cardiomyopathy or other structural abnormalities were not found in any of the carriers. Electrophysiological studies showed that mutant channels were characterised by markedly reduced INa amplitude, a positive shift of voltage-dependence of activation and a substantial negative shift of voltage-dependence of inactivation of INa. From 1978 onwards, a pacemaker for anti-brady pacing was implanted for prevention of sudden death. In patients in whom a prophylactic pacemaker was implanted no unexplained sudden death occurred, whereas 5 sudden deaths occurred in the group of patients who did not receive a pacemaker. CONCLUSION: We have described a large family with a SCN5A-linked disorder (1795insD) with features of LQT3, Brugada syndrome and familial conduction system disease. Anti-brady pacing was successful in preventing sudden death. The mode of death is possibly bradycardic.