Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.     

Heart rate variability and apnea during sleep in Down's syndrome

Autonomic system dysfunction has been reported to occur frequently in patients with Down's syndrome (DS) and is constituted mainly by an imbalance between the sympathetic and vagal systems. The analysis of heart rate variability (HRV) during sleep is a quantitative reliable method for studying such a mechanism, but it has not yet been extensively and adequately applied in DS. In this study, HRV during sleep was evaluated in seven DS patients and in six normal controls, by also controlling for the presence of sleep apnea or arousal. The main results were an increased sympathetic function (low-frequency component of HRV) and a decreased vagal activity (high-frequency component of HRV) in DS with respect to normal controls, during apnea-free periods. Moreover, the presence of apnea, in DS, induced a further significant increase in low-frequency and very low-frequency components of HRV during sleep Stage 2. This study provides additional evidence of a brainstem dysfunctioning in DS, responsible for the abnormal imbalance between the sympathetic and vagal systems and confirms the brainstem involvement already suggested in the literature in order to explain brainstem-auditory evoked potential abnormalities and central sleep apnea in these patients.     

Airway eosinophilia and expression of interleukin-5 protein in asthma and in exacerbations of chronic bronchitis

Background An increased nutnber of eosinophils in the bronchial mucosa has been demonstrated both in asthma and in exacerbations of chronic bronchitis. Oiyective To investigate whether the airway eosinophilia present in asthma and in chronic bronchitis during exacerbations is associated with interleukin (IL)-5 protein expression in the bronchial mucosa. Methods We obtained bronchial biopsies in 18 subjects with asthma (four intrinsic, seven extrinsic and seven occupational) and in II subjects with chronic bronchitis examined during an exacerbation. The findings were compared wilh those of bronchial biopsies from 10 subjects with chronic bronchitis examined under baseline conditions and from seven normal subjects, taken as controls. By immunohistochemistry, we assessed the expression of IL-5 protein and the number of eosinophils (EG2), mast cells ftryptase), and T-lymphocytes (CD3) in the submucosa. Results As compared with controls, the number of eosinophils was increased to a similar degree in both asthma (P < 0.001) and in exacerbations of ehronic bronchitis (P < 0.001). whereas the number of I L-5 immunopositive cells was increased significantly only in asthma (P < 0.01). No diflerences were observed in the number of tnast cells and T-lymphocytes between the four groups of subjects examined. Conciusions This study shows that the degree of airway eosinophilia is similar in asthma and in exacerbations of ehronic bronchitis, but only in asthma is it associated with an increased expression of I L-5 protein in the bronchial tnucosa.     

The effect of glycerol on the guinea-pig hydropic ear

The aim of this paper was to investigate the effect of glycerol on experimental endolymphatic hydrops in guinea-pigs. The right endolymphatic sac and duct were obliterated through an extradural posterior fossa approach. Some animals received a 3 g/kg dose of glycerol for a period of 7 days, whereas others received the same dose for 30 days. The activity of glycerol was studied by investigating the volumetric changes in the scala media determined with a computerized planimeter. Glycerol induced a significant reduction of the hydrops showing its effectiveness and suggesting a strial metabolic response.     

Bile lipid composition and haemostatic variables in a case of high density lipoprotein deficiency (Tangier disease)

A 62-year-old man with clinical and biochemical findings consistent with homozygous Tangier disease is presented. Widespread atherosclerosis was present. Bile lipid analysis showed a low molar percentage of cholesterol with a low saturation index. The data suggest that high density lipoprotein cholesterol may act as a preferential precursor of biliary cholesterol. Coagulation and platelet studies indicated that the patient's platelets were hyper-responsive to aggregating agents and produced an increased amount of thromboxane B2. A platelet storage pool deficiency was also found.     

Patterns of Atrioventricular Conduction During Postexercise Recovery in Patients with Atrial Fibrillation and Wolff-Parkinson-White Syndrome

The effects of the postexercise recovery phase on the functional anterograde conduction properties of the accessory pathway (AP) were evaluated. Twenty-nine patients with Wolff-Parkinson-White (WPW) syndrome were submitted to supine maximal bicycle exercise testing. In seven patients (group I), in whom sustained atrial fibrillation (AF) could be induced by transesophageal pacing (TP), mean ventricular rate (MVR), the shortest R-R interval (SRR) between preexcited beats, and the observed percentage of preexcited beats were evaluated at rest, after each step of exercise and 2 minutes after the end of exercise. In 22 patients (group II), in whom sustained AF could not be induced, decremental TP was performed to evaluate the shortest atrial cycle length (SCL) with 1:1 conduction over AP at rest, after each step of exercise, and 2 minutes after the end of exercise. In four patients in group I, the protocol was repealed with atropine injected during the last minute of exercise. In 12 patients (three from group I and nine from group II), catecholamine plasma levels were measured at rest, at peak exercise, and during recovery. MVR was 144 ± 20 beats/min at rest, 186 ± 21 beats/min at peak exercise (P < 0.001 vs rest), and 179 ± 21 beats/min during recovery (P < 0,001 vs rest; P < 0.05 vs peak exercise). SRR was 289 ± 73 msec at rest, 223 ± 25 msec at peak exercise (P < 0.05 vs rest), and 227 ± 29 msec during recovery. Preexcited beat percentage was 95.4 ± 12 at rest, 35.2 ± 24.2 at peak exercise (P < 0.001 vs rest), and 85.1 ± 22.5 during recovery fP < 0.01 vs peak exercise and n.s. vs rest). In patients in whom atropine was injected MVR was 139 ± 17 beafs/min at rest, 184 ± 19 beats/min at peak exercise (P < 0.05 vs rest), and 172 ± 16 beats/min during recovery (P < 0.05 vs peak exercise, P < 0.05 vs rest); SRR was 320 ± 71 msec at rest, 225 ± 25 msec at peak exercise, and 232 ± 3 inset; during recovery; preexcited beat percentage was 99 ± 1 at rest, 26 ± 18 at peak exercise (P < 0.01 vs rest), and 28 ± 20 during recovery (NS vs peak exercise, P < 0.01 vsrest). In group II. mean sinus rate was 84 ± 12 beats/min at rest, 151 ± 15 beats/min at peak exercise, and 117 ± 21 beats/min 2 minutes after the end of exercise; mean SCL was 328 ± 75 msec at rest, 273 ± 76 msec at peak exercise (P < 0.0001 vs rest), and 280 ± 79 msec during recovery (P < 0.0001 vs rest and NS vs peak exercise). Mean epinephrineand norepinephrine plasma levels (12 patients from groups I and II) were; 4 7.9 ± 76.6 and 355.5 ± 185.1 pg/mL at rest; 193.0 ± 88.0 and 823.9 ± 390.3 pg/mL at peak exercise (P < 0.0001 vsrest); 148.5 ± 94.5 and 672.7 ± 272.3 during recovery (P < 0.001 vs rest; P < 0.01 vs peak exercise). Thus, during early recovery versus peak exercise: SCL and SRR are still lower and confirm the persistence of increased AP conductivity; in patients with atrial fibrillation preexcited beat percentage is markedly enhanced while the duration of preexcited complexes is increased and MVR is still high. The poslexercise recovery phase in patients with WPWand atrial fibrillation determines a higher ventricular response rate with major preexcitation than does rest and peak exercise. The fact that atropine prevents increases in preexcited beats percentage demonstrates that the underlying electrophysiological basis is a discordance of autonomic effects on the conduction properties of the two afrioventricular pathways.