Safety of Deferring the Reimplantation of Pacing Systems After Their Removal for Infectious Complications in Selected Patients: A 1‐Year Follow‐Up Study

Introduction: Recent expert consensus guidelines mention that one of the principles for infected device replacement following removal is to “reevaluate carefully if there is a continued need for a new cardiac device replacement.” This is a Class I recommendation, which nevertheless suffers from a very low level of evidence (level of evidence C), since no study has revisited the systematic practice of reimplanting the same device based on a meticulous clinical reassessment. In the present paper, we examined the safety of withholding the implantation of pacing systems in selected patients. Methods and Results: Between January 2005 and December 2007, 188 consecutive patients underwent extractions of infected pacing systems at 2 medical centers. “Low‐risk” patients were identified by (1) a spontaneous heart rate >45 bpm, (2) no symptomatic asystole during monitoring, (3) QRS duration <120 ms when history of AV block was noted, (4) no high‐degree AV block during continuous monitoring. They remained device‐free, unless an adverse clinical event occurred mandating the reimplantation. The primary study endpoint was rate of sudden death and syncope after a 12‐month follow‐up. Among the 74 (39.4%) “low‐risk” patients, a single patient suffered a bradycardia‐related syncopal event corresponding to a 1.3% (95% CI, 0.0–3.9) rate of primary endpoint. Pacing systems were also reimplanted in 24 patients (32.4%) for syncope (n = 1), nonsevere bradycardia‐reated symptoms (n = 17), cardiac resynchronization (n = 2), and for reassurance in 4 asymptomatic patients. Conclusion: After removal of infected pacing systems, these preliminary data demonstrated that a strategy of nonsystematic device reimplantation associated with close surveillance was safe in “low‐risk” patients, allowing the administration of antimicrobials in a device‐free state. (J Cardiovasc Electrophysiol, Vol. 21, pp. 540‐544, May 2010)     

Basic Rules of Dosimetry in Endovascular Brachytherapy

Endovascular brachytherapy after percutaneous coronary intervention (PCI), is becoming a standard approach for the treatment and prevention of restenosis. A variety of technical approaches are currently available to deliver ionizing irradiation to the vascular target. Basically two kinds of radioactive isotopes are available that emit gamma radiation (photons) or beta radiation (electrons). The pitfalls and solutions for the optimization of dosimetry are discussed. As might be expected, the inhomogeneous dose distribution across the target volume results in recurrence by underdosage or in complications because of overdosage. Moreover, uniformization of the target definition and reporting of the dose distribution in endovascular brachytherapy is a prerequisite for comparison between the results of the various clinical trials and is absolutely necessary to improve the therapeutic efficacy of this new approach in the prevention of restenosis after coronary angioplasty with or without stenting.     

Haemodynamic effects of molsidomine and propranolol in patients with cirrhosis

Propranolol and molsidomine have both been shown to decrease the hepatic venous pressure gradient in patients with cirrhosis. The present study aimed at assessing the effects of the combination of these two drugs on splanchnic and systemic haemodynamics of cirrhotic patients. Fifteen patients with biopsy proven alcoholic cirrhosis had haemodynamic measurements under basal conditions, 60  min after oral administration of 4  mg molsidomine then 15  min after intravenous administration of 15  mg propranolol. As compared with baseline values, molsidomine was found to decrease mean arterial pressure (−7.9%, P <0.01), cardiac output (−7.3%, P <0.01), pulmonary wedged pressure (−45.8%, P <0.05) and hepatic venous pressure gradient (−11.7%, P <0.01). Propranolol decreased heart rate (−21%, P <0.01), further decreased cardiac output (−20.6%, P <0.01) and hepatic venous pressure gradient (−10.5%, P <0.01). As a whole, molsidomine plus propranolol decreased mean arterial pressure (−8%, P <0.01), heart rate (−19%, P <0.01), cardiac output (−26.5%, P <0.01) and hepatic venous pressure gradient (−21%, P <0.01). Pulmonary wedged pressure, liver blood flow and hepatic intrinsic clearance of indocyanine green were not significantly changed by the association of molsidomine and propranolol. We conclude that in patients with cirrhosis, molsidomine and propranolol potentiate their effects on hepatic venous pressure gradient. Such a combination could therefore prove useful in the treatment of portal hypertension.     

Synthesis and Biological Evaluation of New 3-Aralkylamino-2-aryl-2H-1,2,4-pyridothiadiazine 1,1-dioxides as Potential CCK-Receptor Ligands

A series of 2-aralkyl-4H-pyridothiadiazine 1,1-dioxides and 3-aralkylamino-2-aryl-2H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides structurally related to quinazolinone CCK receptor antagonists were synthesized and evaluated as CCK-A and CCK-B receptor ligands. The compounds were effective as cholecystokinin-ligands in the micromolar range of concentration, c.f. the cholecystokinin receptor antagonists asperlicin, lorglumide or benzotript, and were thus less potent than the best quinazolinones previously reported. Although the compounds were unsuitable for drug use, the work contributed to our understanding of the chemistry of unusual 2,3-disubstituted pyridothiadiazinedioxides.     

Importance of Atrial Contraction in Hypertrophic Obstructive Cardiomyopathy: Implications for Pacing Therapy

Hypertrophic cardiomyopathy is a primary myocardial disease characterized anatomically by left ventricular (LV) asymmetric hypertrophy and pathophysiologically by normal or even supernormal systolic ejection performance contrasting with impaired diastolic function. Altered ventricular relaxation tends to reduce the contribution of rapid ventricular filling to total LV filling volumes. Consequently, the contribution of left atrial (LA) contraction can be significantly increased. In some patients LV filling, and thus stroke volume, critically depend upon atrial systole. These data may have important clinical implications especially in patients treated with permanent cardiac pacing. Preserving a fully efficient LA contribution to LV filling is probably a key point in those patients .     

Isolation,sequence, and conformation of seven trichorzianines from Trichoderma harzianum

From the antagonistic fungus Triclroderma harzianum, a group of acidic new peptides, trichorzianines B (TB), was isolated in addition to neutral trichorzianines A (TA) previously studied. TA and TB exhibit various biological activities related to their membrane properties and a different behaviour of the two groups was noticed. As observed for other peptaibols, TB consist in a microheterogeneous mixture which was resolved into pure peptides by reversed-phase C18 HPLC. The sequence of the seven main isolated TB, namely TB IIa, TB IIIc, TB IVb. TB Vb. TB VIa. TB VIb, TB VII, was determined by the combined use of positive ion FAB mass spectrometry and 2D ¹H n.m.r. spectroscopy, including COSY and NOESY experiments. TB differ from the corresponding TA only by the replacement of Gln 18 in the TA sequence by a glutamic acid. The ¹H n.m.r. data suggested that the TB are mainly organized in an α helix.     

Long-Term Survival After Closed-Chest His-Bundle Ablation with DC Shock for Supraventricular Arrhythmias: A 10-Year Experience with 317 Consecutive Patients

Survival after closed-chest ablation of His bundle with DC shock for supraventricular arrhythmias was analyzed for a 10-year period (May 1982-December 1992) with 317 consecutive patients (167 males, 150 females; mean age 66 years; range 33–93 years). Of these, 54 patients died (17.3%) and 5 were lost to follow-up. The mean age at ablation was 70.3 ± 8.3 years with a range of 49–93 years. Of those who died, the mean survival was 30.5 ± 28.6 months with a range of 36 hours to 120 months; the diagnosis of heart disease was; hypertension (n = 14), cardiomyopathy (n = 8), ischemic (n = 7), valvular (n = 6). Cor pulmonale (n = 3), valvular and ischemic (n = 2). hypertension and ischemic (n = 1), miscellaneous (n = 3), and none (n = 10). Of the patients who died after ablation, the arrhythmias at the time of the ablation were atrial fibrillation (AF; n = 33), sick sinus syndrome (n = 5), atrial flutter (AFL; n = 4), paroxysmal AV junctional tachycardia (PAVJT; n = 4), AF + AFL (n = 4), atrial tachycardia (n = 2). PAVJT + AFL (n = 1), and AF + AFL + atrial tachycardia (n = 1). Death was sudden in 13 patients (25%), due to heart failure in 10 (19.2%), myocardial infarction in 4 (7.7%), stroke in 4 (7.7%). aortic vascular accident in 3 (5.8%), miscellaneous in 18 (34.6%), and undetermined in 2. The overall survival rate was 94.5% at 1 year (n = 256), 80.1% at 5 years (n = 88), 72.8% at 8 years (n = 20), and 51% at 10 years (n = 4); patients with no underlying heart disease had a better survival. DC ablation of the His bundle was not associated with a high short- or long-term mortality. This study may serve as a historical review with which to compare closed-chest ablation of the His bundle with that of other energy sources such as radiofrequency energy.     

Effects of a combination of napping and bright light pulses on shift workers' sleepiness at the wheel: a pilot study

To assess the effects of napping + bright light on shift work drivers sleepiness at the wheel, we performed a pilot study on nine shift workers on three shifts (morning, afternoon, night), driving on a private road circuit. Sleepiness at the wheel was measured by ambulatory polysomnography and assessed using 30‐s segments of recordings with a percentage of theta electroencephalogram of at least 50% (15 s) of the period recorded. Sleepiness was also assessed by the Stanford Sleepiness Scale (SSS). Participants drove the same car on two similar 24‐h periods of work, with three drivers in each shift (morning, afternoon, night), separated by 3 weeks. During the baseline period, the subjects were told to manage their rest as usual. During the second experimental period, they had to rest lying in a dark room with two naps of 20 min and then exposed to bright light (5000 lux) for 10 min. Subjects showed a significantly decreased sleepiness at the wheel with an average of 10.7 ± 6.7 episodes of theta sleep during the baseline (766 ± 425 s) versus 1.0 ± 1.0 episode lasting 166 ± 96 s during the second period (P = 0.016; P = 0.0109). The percentage of driving asleep was also significantly reduced (3.7% ± 1.9% versus 0.9% ± 0.6%, P = 0.0077). The average SSS score in the group decreased from 2.76 ± 1.27 to 2.28 ± 0.74 (P = 0.09). In this pilot and preliminary study, a combination of napping and bright light pulses was powerful in decreasing sleepiness at the wheel of shift work drivers.     

Cardiac Arrhythmias and the Autonomic Nervous System

Cardiac Arrhythmias and the Autonomic Nervous System. The multiple facets of cardiac arrhythmias and their relationship with the autonomic nervous system can be investigated by studying the spontaneous heart rate behavior through ambulatory ECG recordins, an approach that complements the limitations of invasive electrophysiologic investigations. Information obtained from heart rate behavior is more reliable in the absence of structural heart disease and ventricular hypertrophy/failure, during which compensatory mechanisms involving the autonomic nervous system tend to limit reflex changes in heart rate. Thus, in such situations, less marked sinus rhythm variations preceding the arrhythmia onset do not imply a more limited influence of the autonomic nervous system, and the sensitivity of the electrophysiologic substrate may otherwise vary. These two factors may combine to form the basis of the adrenergic paradox¹¹ that implies that the more marked the autonomic nervous system dependence of tachyarrhythmias, the less obvious its evidence. Assessment of the QT interval dynamicity may also allow one to evaluate the modulation of autonomic neural effects on the ventricular tissues. Finally, it may be difficult to distinguish clearly autonomic nervous system dependence from rate dependence: the latter frequently conditions the behavior of the trigger whereas the former mainly concerns the electrophysiologic substrate. There are many examples of the importance of the autonomic nervous system as a determinant of cardiac arrhythmias. In the atrium, either limb of the autonomic nervous system, particularly the parasympathetic limb, can generate atrial fibrillation. The absence of structural heart disease defines pure electrophysiologic substrates responsible for benign forms of ventricular tachycardia as welt as potentially lethal tachyarrhythmias of the long QT syndrome and its variants. In both, the role of the autonomic nervous system is essential, although the therapeutic consequences are crucial only in the latter. In the presence of heart disease and, in particular, heart failure, the autonomic nervous system behavior is more difficult to assess than in the absence of structural heart disease. This does not mean that its role is less crucial. In this situation the beneficial effects of beta blockers may be as important as in normal hearts although physicians should be more cautious when heart failure is present.