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.     

PLASMA INSULIN DISAPPEARANCE CURVE AFTER INTRAVENOUS INSULIN INJECTION IN HUMAN HYPERTHYROIDISM

The disappearance curves of plasma insulin after intravenous injection of unlabelled pork insulin was studied in nine young female hyperthyroid subjects with Graves' disease and eleven young female normal subjects, who served as controls. Comparison of the curves by analysis of variance did not reveal statistical differences between them (F obtained = 2.8, F F 0.05 = 4.41), implying that there was no significant differences in the transference of injected insulin from plasma to the extra-vascular space between hyper- and euthyroid subjects. The results may suggest that the metabolism of insulin is not appreciably affected in hyperthyroidism.     

THE HYALINE MEMBRANE DISEASE–INTRAVENTRICULAR HEMORRHAGE RELATIONSHIP IN THE VERY LOW BIRTH WEIGHT INFANT: PERINATAL ASPECTS

ABSTRACT. A large retrospective clinical study is reported confirming pathologic studies upon the effect of hyaline membrane disease on the occurrence of intraventricular hemorrhage in very low birth weight infants. Two hundred and twenty infants with birth weight 1500 g and gestational age 32 weeks were studied. Infants with hyaline membrane disease (112) had 56 % incidence of intraventricular hemorrhage whereas of those without hyaline membrane disease (108) only 31% developed intraventricular hemorrhage ( p < 0.001). When controlled for gestational age, the more immature infants ( 1000 g) exhibited no difference in the occurrence of intraventricular hemorrhage whether hyaline membrane disease coexisted or not. In the 1001–1500 g group, the occurrence of hyaline membrane disease with intraventricular hemorrhage was significant ( p < 0.001). The association of lower Apgar scores and the influence of intermittent positive pressure ventilation in infants with intraventricular hemorrhage is discussed. Extreme immaturity negates all perinatal clinical expertise in determining neonatal outcome. Therefore, carrying pregnancies beyond 28 weeks gestation is mandatory. Beyond 28 weeks, pulmonary maturity and the influence of therapeutic modalities and maternal transport become increasingly important.     

Optimization of Pacing Algorithms to Prevent and Treat Supraventricular Tachyarrhythmias

Preventive atrial pacing and antitachycardia pacing have been proposed for the treatment of atrial fibrillation and associated arrhythmias in patients with indications for device implantation. Preventive algorithms provide overdrive atrial pacing, reduction of atrial premature beats, and prevent short-long atrial cycles with good patient tolerance. However, clinical trials testing preventive algorithms have shown contradictory results, possibly because of different trial designs, end points and patient populations. Factors probably responsible for neutral results include an already high atrial pacing percentage with the conventional DDDR mode, suboptimal atrial pacing site, and the deleterious effects of high percentages of right ventricular apical pacing. Atrial antitachycardia pacing therapies are effective in treating organized atrial tachyarrhythmias (that precede atrial fibrillation), mainly when delivered early after the onset particularly if the tachycardia is relatively slow. Antitachycardia pacing therapies might influence atrial fibrillation burden, but clinical studies have shown conflicting results about this issue. Consistent monitoring of atrial and ventricular rhythm including progression to persistent forms of atrial arrhythmias, variability of atrial arrhythmia recurrence patterns and onset mechanisms as well as antitachycardia pacing efficacy should be recorded in the stored device memory and used for optimal individual programming of these new functions.     

Ventricular Cross Stimulation in a Dual Chamber Pacing System: Phenomenon Analysis

Seven cases of ventricular cross stimulation from a group of 23 patients implanted with DDD devices are presented. In two patients the phenomenon was observed at the moment of DDD programming at nominal values, and in five other patients it was reproduced by increasing the atrial output voltage up to ten volts. In all 23 patients cross stimulation disappeared permanently within 24 hours after implantation. From the onset of cross stimulation to its end, atrial and ventricular threshold voltages were unchanged, while the atrial and ventricular impedances significantly decreased. These results suggest that an important role in the phenomenon occurs by impedance variation at the interface between the pulse generator and body tissue.     

Duplex-Doppler assessment of cirrhosis in patients with chronic compensated liver disease

Portal venous flow velocity (PFV) was measured with duplex-Doppler equipment in 50 normal subjects and in 117 patients with suspected chronic liver disease who showed no evidence of decompensation such as ascites, hepatic encephalopathy, jaundice or oesophageal bleeding. All the patients underwent percutaneous liver biopsy which demonstrated non-cirrhotic liver disease in 58 cases (CH-patients: steatosis 8, persistent chronic hepatitis 8, active chronic hepatitis 42) and liver cirrhosis in the other 59 cases (LC-patients). The normal subjects and the CH-patients had similar values of max-PFV and mean-PFV (max-PFV 26.7±3.2 and 25.7±3.4 cm/s respectively; mean-PFV 22.9±2.8 and 22.4±3.8 cm/s respectively). The LC-patients’ values (max-PFV 19.3±3.5; mean-PFV 16.9±2.9) were significantly lower than those of the normal subjects (P<0.001) and of the CH-patients (P<0.001). Considering the normal max-PFV to be in the range 20–33.1 cm/s (mean±2 s.d. of the normal subjects, 95% confidence limits), max-PFV was reduced in 0/50 normal subjects, 1/58 CH-patients and 39/59 LC-patients (66.1% sensitivity; 98.2% specificity). In conclusion, the duplex-Doppler measurement of PFV is of great interest in the diagnostic study of patients with suspected chronic compensated liver disease and in the early diagnosis of cirrhosis. A low max-PFV is a reliable pointer to liver cirrhosis, whereas a normal max-PFV indicates a non-cirrhotic liver disease but is less probative. Each centre should standardize normal PFV values in order to establish their own threshold value for diagnosing liver cirrhosis.     

Home Monitoring in Patients with Implantable Cardiac Devices: Is There a Potential Reduction of Stroke Risk? Results from a Computer Model Tested Through Monte Carlo Simulations

Introduction: Patients with pacemakers and implantable defibrillators (ICD) may experience asymptomatic atrial fibrillation (AF), detected with a delay depending on the in-person follow-up schedule. Home monitoring (HM) remote control with automatic alerts for AF may drive early anticoagulation, potentially reducing stroke risk.
Methods and Results: A sample of 136 pacemaker (103) and ICD (33) patients with or without cardiac resynchronization therapy not taking anticoagulation at implant were monitored remotely with HM. Upon HM alerts for AF, patients were recalled to update therapy. Two-year data were entered in a computer Monte Carlo model, simulating 4,000 virtual subjects with the same AF and CHADS₂ stroke risk distribution of our real population. Simulations reproduced a 2-year follow-up. Two thousand subjects were supposed to be followed with HM (HM group) and 2,000 with standard in-person follow-up (SF group) at 3, 6, 9, or 12 months.
Two-year Kaplan-Meier cumulative probability of ≥24-hour AF was 15.6% (95%CI 8.5–23.3%); the AF-related symptom rate was 27% and the median CHADS₂ score was 2. As a result of simulations, stroke incidence in case of AF was 2.3 ± 1.1% in the HM group and 2.4 ± 1.1%, 2.5 ± 1.2%, 2.7 ± 1.2%, and 2.9 ± 1.3% in the SF group with 3-, 6-, 9-, and 12-month follow-up programs, with odds ratios of 0.97 (95%CI 0.93–1.01), 0.91 (0.88–0.95), 0.87 (0.84–0.90), and 0.82 (0.79–0.85) (HM better if odds ratios <1), respectively.
Conclusions: Daily HM potentially reduces the stroke risk by 9% to 18% with respect to SF with intervisit intervals of 6 to 12 months.     

UMBILICAL CORD CORTISOL AND PROLACTIN LEVELS IN PRETERM INFANTS

ABSTRACT. The influence of labor and route of delivery upon the umbilical cord serum levels of cortisol and prolactin in ninety-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A) presented a higher mean cord cortisol concentration than those delivered by cesarean section (group B); mean prolactin values, however, were not different between both groups. Although there was no difference in cortisol and prolactin levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I) and those without labor (group B-II), the mean cortisol concentration was significantly higher in group A than in group B-I. The mean prolactin levels did not differ among all the studied groups. It is concluded that there is no association between presence of labor or route of delivery and cord seum levels of prolactin, there is no association between spontaneous preterm labor and cord cortisol values and there is an association between vaginal delivery and high cord cortisol levels in preterm infants. It is suggested that the increase in serum cortisol levels does not precede the initiation of preterm parturition but it is secondary to the stress caused by vaginal delivery.     

Effect of Steroid Eluting Versus Conventional Electrodes on Propafenone Induced Rise in Chronic Ventricular Pacing Threshold

The aim of this study was to evaluate chronic ventricular pacing threshold increase after oral propafenone therapy. Eighty-three patients affected by advanced atrioventricular hJock and sick sinus syndrome were studied at least 3 months after pacemaker implantation, before and after oral propafenone therapy (450–900 mg/day based on body weight). The patients were subdivided into three groups according to the type of unipolar electrode that was implanted: group I (41 patients)Medtronic CapSure 4003, group II(30 patients)Medtronic Target Tip 4011, and group III (12 patients)Osypka Vy screw-in lead. In all cases a Medtronic unipolar pacemaker was implanted: 30 Minix, 23 Activitrax, 14 Elite, 12 Legend, and 4 Pasys. Propafenone biood level was measured in 75 patients 3–5 hours after propafenone administration. The pacing autothreshoid was measured at 0.8 V, 1.6 V, and 2.5 V by reducing puise width. At the three different outputs before and after propafenone, threshold increments were significantly lower in group I in comparison with group II and group III (propafenone ranging from < 0.001 to < 0.05). No significant difference was found in pacing impedance or in propafenone plasma concentration in the three groups. Strength-duration curves were drawn for each group at baseline and after propafenone administration. Before propafenone, in group I, the knee was markedly shifted to the left and downward as compared to the classic curve, so that the steep part was predominant; in group II and group III this shift was progressively less evident. After propafenone we found the curve shifted to the right with the flat part progressively more evident in group II and group III as compared to group I. We conclude that steroid eiuting leads cause less threshold increase than conventionol and screw-in ones after oral propafenone, thus leading to safer chronic pacing. Chronic pacing at 2.5-V amplitude and 0.6-msec width was feasible in 97% of group I patients and in 80% of group II patients, but not in group III due to an insufficient safety margin. propafenone, pacing threshold