J. Haaksma

Prospective Evaluation of Early Cardiac Damage Induced by Epirubicin-Containing Adjuvant Chemotherapy and Locoregional Radiotherapy in Breast Cancer Patients

PURPOSEnTo evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients.nnnPATIENTS AND METHODSnPatients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction.nnnRESULTSnNo patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV.nnnCONCLUSIONnRelatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.

Psychobiological Characteristics of Dissociative Identity Disorder: A Symptom Provocation Study

BACKGROUNDnDissociative identity disorder (DID) patients function as two or more identities or dissociative identity states (DIS), categorized as neutral identity states (NIS) and traumatic identity states (TIS). NIS inhibit access to traumatic memories thereby enabling daily life functioning. TIS have access and responses to these memories. We tested whether these DIS show different psychobiological reactions to trauma-related memory.nnnMETHODSnA symptom provocation paradigm with 11 DID patients was used in a two-by-two factorial design setting. Both NIS and TIS were exposed to a neutral and a trauma-related memory script. Three psychobiological parameters were tested: subjective ratings (emotional and sensori-motor), cardiovascular responses (heart rate, blood pressure, heart rate variability) and regional cerebral blood flow as determined with H(2)(15)O positron emission tomography.nnnRESULTSnPsychobiological differences were found for the different DIS. Subjective and cardiovascular reactions revealed significant main and interactions effects. Regional cerebral blood flow data revealed different neural networks to be associated with different processing of the neutral and trauma-related memory script by NIS and TIS.nnnCONCLUSIONSnPatients with DID encompass at least two different DIS. These identities involve different subjective reactions, cardiovascular responses and cerebral activation patterns to a trauma-related memory script.

Evidence for differential sympathetic and parasympathetic reinnervation after heart transplantation in humans

During heart transplantation (HTX) all neural connections are severed. In humans, signs of autonomic reinnervation have been found. In this study non-invasive tests were used to compare signs of sympathetic and parasympathetic reinnervation. Non-invasive autonomic function tests and heart rate variability parameters (HRV; 24 h electrocardiographic registration) were used to investigate signs of reinnervation. 16 HTX patients (14 males) were compared with age-and sex-matched controls. Parasympathetic heart rate changes in HTX compared to controls were attenuated during the diving test, deep breathing, the Valsalva maneuver and standing up but not during carotid sinus massage. Sympathetic heart rate increases were lower during the cold pressor test and mental stress. The blood pressure responses were comparable to the control group, but not during active standing and tilting. This finding suggests an obligatory blood pressure role for the innervated heart in these two tests. All HRV parameters were lower in HTX. One or more normal parasympathetic responses were found in 13 out of 16 patients versus 4 out of 16 with normal sympathetic responses (p < 0.05). Heart rate variations were less in case of a higher donor age, and higher in case of a longer time after HTX. Parasympathetic signs of reinnervation are more common than sympathetic signs of reinnervation. A higher donor age reduces signs of reinnervation. If the sympatho-vagal balance is a prognostic factor in HTX patients as it is in other cardiac diseases these findings are clinically relevant.

Pharmacological treatment of young children with permanent junctional reciprocating tachycardia.

Our objective was to assess the efficacy of pharmacological treatment in reducing the incidence of permanent junctional reciprocating tachycardia in young children, or to bring the mean heart rate over 24 h to a normal level. We included 21 children with a median age of 0.05 year seen with permanent junctional reciprocating tachycardia over the period 1990 through 2001. Of these children, two had abnormal left ventricular function. Follow-up visits were made at least every 6 months. We registered the presence of the tachycardia over 24 h, the mean heart rate over 24 h, and cardiac function. Treatment was started with propafenone alone, or in combination with digoxin as the first choice. Treatment was effective in 14 cases (67%), with either complete disappearance of the tachycardia after discontinuation of medication, or continuation in sinus rhythm with medication; partially effective in 4 cases (20%) when the mean heart rate over 24 h on the last Holter recording was less than 1 standard deviation above the normal for age; but was not effective in the remaining 3 cases (14%). In 3 patients treated with propafenone, or 13 given propafenone and digoxin, treatment was effective in 12 (75%), partially effective in 2 (13%), and ineffective in the other 2 (13%). All 21 children had a normal left ventricular function at the end of follow-up. The median duration of follow-up was 2.4 years. Permanent junctional reciprocating tachycardia had disappeared spontaneously in one-third of the children, 5 being less than 1 year old. Adverse effects, seen in 5 cases, were mild or asymptomatic. No signs of proarrhythmia were registered. Pharmacological treatment, either with propafenone alone, or in combination with digoxin, is safe and effective in young children with permanent junctional reciprocating tachycardia. The mean heart rate is normalized, and cardiac function is restored and preserved. Radiofrequency ablation may be delayed to a safer age, with the arrhythmia disappearing spontaneously in one-third.

Rhythmic ECG Changes in a Patient with Long QT Syndrome Type 3

A healthy 71-year-old female was investigated because she was a member of a previously reported large family with long QT syndrome type 3 and carrier of the mutant gene (SCN5A, 1795insD).1,2 On a 24-h Holter recording, we noticed prolonged episodes during the early morning hours (while the patient was asleep), with rhythmic changes in T-wave morphology; in recurrent cycles of three beats, Twave morphology ranged from two predominantly biphasic T-waves to a large negative T-wave (Fig. 1). On closer inspection, QRS-amplitude also exhibited subtle rhythmic changes. Given the fact that heart rate was around 48 beats/min, the number of cycles would be 16 per minute, corresponding with a frequency of 0.27 Hz. We then reasoned that a respiratory effect might play a role in mediating the rhythmic T-wave and QRS changes. To investigate this possibility, we performed analysis of heart rate variability, in particular, spectral analysis (Fig. 2). We found that the episodes with the rhythmic T-wave and QRS changes were exactly parallel in terms of the location of the high frequency peak (at 0.26 to 0.28 Hz), indeed suggesting that respiration played a mediating role.

The Psychobiology of Dissociative Identity Disorder

Traumatic stress studies have focused on post-traumatic stress disorder (PTSD). Characteristic cerebral, endocrine, and cardiovascular responses of patients with PTSD to external stress stimuli have been reported (e.g. Rauch et al. 2003; Tanev 2003). Functional neuroimaging of PTSD has revealed abnormalities in functional connectivity, regional volume and regional cerebral blood flow (rCBF) in several brain structures (see for examples and recents reviews: Lanius et al. 2004; Tanev 2003; Vermetten and Bremner 2003).

The dimension of 2D and 3D Poincare plots obtained from 24 hour ECG registrations

The dimension is a basic concept in non linear dynamics. The box counting dimension (BCD) is one of the methods that is available to determine the dimension. We studied the dimension of the heartrate signal in both 2 and 3D Poincare plots in a group of twenty five post myocardial infarction (MI) patients together with an age and sex matched control group. The average BCD from the normal subjects based on a 2D first return plot was 1.46/spl plusmn/0.09, while in the infarction group this was significantly lower: 1.34/spl plusmn/0.17 (p=0.003). Excluding ectopic data from the analysis caused large changes in the resulting dimension.