Upgrade to biventricular pacing in patients with pacing-induced heart failure: can resynchronization do the trick?

Dyssynchrony imposed on ventricular function by right ventricular (RV) apical pacing may lead in some cases to worsening or appearance of heart failure (HF) symptoms. This is a result of an altered pattern of activation, leading to several histological and functional adjustments of the left ventricle, including inhomogeneous thickening of the ventricular myocardium and myofibrillar disarray, fibrosis, disturbances in ion-handling protein expression, myocardial perfusion defects, alterations in sympathetic tone and mitral regurgitation. Studies of mid- and long-term effects of RV apical pacing on left ventricular (LV) function have demonstrated a progressive decline in ejection fraction and other indices of LV functional competence. Upgrading RV pacing systems to biventricular resynchronization modalities is a theoretically promising option for paced patients with worsening HF. The potentially favourable effect of upgrading on LV functional indices and patient clinical status has been demonstrated in few, non-randomized trials. Apart from the scantiness of existing clinical data, issues concerning technical aspects of the procedure and selection of eligible patients are raised. Is pacing-induced dyssynchrony equivalent to the indigenous dyssynchrony in unpaced patients with HF? What selection criteria should be applied in order to identify potential responders to cardiac resynchronization therapy in this patient population? Answers to these and more questions are still lacking.     

Duration of salmeterol-induced bronchodilation in mechanically ventilated chronic obstructive pulmonary disease patients: a prospective clinical study

Introduction

Delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer device in mechanically ventilated patients has become a widespread practice. However, except for the short-acting β2-agonist salbutamol, the duration of action of other bronchodilators, including long-acting β2-agonists, delivered with this technique is not well established. The purpose of this study was to examine the duration of bronchodilation induced by the long-acting β2-agonist salmeterol administered with an MDI and a spacer in a group of mechanically ventilated patients with exacerbation of chronic obstructive pulmonary disease (COPD).

Methods

Ten mechanically ventilated patients with acute exacerbation of COPD received four puffs of salmeterol (25 μg/puff). Salmeterol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud enhance spacer. Static and dynamic airway pressures, minimum (R_int) and maximum (Rrs) inspiratory resistance, and the difference between Rrs and R_int (ΔR) were measured before and at 15, 30, and 60 minutes as well as at 2, 3, 4, 6, 8, 10, and 12 hours after salmeterol administration. The overall effects of salmeterol on respiratory system mechanics and heart rate during the 12-hour study period were analyzed by nonparametric Wilcoxon signed rank test.

Results

Salmeterol caused a significant decrease in dynamic and static airway pressures, R_int, and Rrs. These changes were evident at 30 minutes and remained significant for 8 hours after salmeterol administration. The duration of bronchodilation varied significantly among patients, lasting in some patients more than 10 hours and wearing off in others in less than 6 hours.

Conclusions

It is concluded that four puffs of salmeterol delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD exacerbation, the duration of which is highly variable, precluding definite conclusions in regard to optimum dosing schedules.     

Heart rate lowering by inhibition of the pacemaker current: a new therapeutic perspective in cardiovascular disease

Several studies have demonstrated that resting heart rate is an important correlate of cardiovascular and all-cause mortality and that the mortality benefit of some cardiovascular drugs seems to be related in part to their heart rate-lowering effects. Since the currently available classes of drugs with heart-rate lowering effect (e.g. beta-blockers and calcium channel antagonists) also exert multiple structural and functional actions on the cardiovascular system, which may be in some cases undesired, the introduction of a new class of agents exclusively affecting the pacemaker activity of the sinus node is of particular interest. The first molecule of this class - sinus node modulators or I(f)-current inhibitors - to reach clinical application is ivabradine. Cardiac pacemaker cells generate a spontaneous slow diastolic depolarisation that drives the membrane voltage away from a hyperpolarised level towards the threshold level for initiating a subsequent action potential, generating rhythmic action potentials that propagate through the heart and trigger myocardial contraction. The I(f) current is an inward ionic current that determines the slope of diastolic depolarisation, which in turn controls the heart beating rate. Extensive work has amply demonstrated its involvement in the generation of spontaneous activity. The molecular basis of the generation of the pacemaker current was landmarked by the cloning of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, which constitute the structural units of the f-channels. This review addresses the major basic properties of cardiac f-channels, with a focus on the mode of action of I(f)-current inhibitors and outlines the therapeutic implications of the existing research data.     

Improved myocardial performance during repetitive exercise testing: the role of extracellular superoxide dismutase activity in a model of exercise-induced myocardial preconditioning

Background

The aim of this study was to investigate whether endogenous antioxidant defense is involved in adaptation to myocardial ischemia in patients with coronary artery disease and severe exercise-induced myocardial ischemia.

Methods

Fifty patients, aged 50 to 72 years (mean, 58 ± 6 years), with positive exercise test results underwent 4 treadmill exercise tests. Thallium-201 scintigraphy was performed during the first and the fourth testing. The second, the third, and the fourth tests were performed the next day. The time interval between the second and the third test was 15 minutes, and between the third and the fourth test, the interval was 45 minutes. Extracellular superoxide dismutase activity was measured just before and at the peak of the first and the fourth exercise test.

Results

The patients were divided in 2 groups according to the extent of myocardial ischemia at peak exercise of the fourth test compared with the first test. Most of the patients studied (37/50) showed improved myocardial performance during the last of the sequential exercise tests, as demonstrated with the studied exercise parameters and the extent of myocardial ischemia in thallium-scintigraphy. Extracellular superoxide dismutase activity before the last exercise test was found to be significantly increased only in the patients who had improved myocardial performance at the last of the sequential exercise tests.

Conclusion

The beneficial effects of sequential episodes of exercise-induced myocardial ischemia seem to be strongly related to extracellular superoxide dismutase activity. Although there is still lack of direct evidence, our data support the theory that the favorable adaptation to repetitive exercise may represent an aspect of the clinical relevance of ischemic preconditioning in humans.     

Increased variance of P wave duration on the electrocardiogram distinguishes patients with idiopathic paroxysmal atrial fibrillation

We hypothesized that the variance of P wave duration (P variance) in the 12-lead ECG could reflect the spatial dispersion of P wave duration due to inhomogeneous and delayed propagation of sinus impulses in the atria, and moreover could present better reproducibility than maximum P wave duration and P wave dispersion that have already been used for the prediction of idiopathic paroxysmal AF. We also tested a semiautomated PC-based method to improve the accuracy and reproducibility of P wave measurements. A 12-lead ECG was obtained from 60 patients with idiopathic paroxysmal AF and from 50 healthy controls. All ECGs were analyzed manually using magnifying lens and calipers, while 20 randomly selected ones were scanned and analyzed on screen using common commercial software. P maximum, P dispersion, and P variance were all significantly higher in patients with paroxysmal AF than in controls. A P maximum value of 110 ms, a P dispersion value of 40 ms, and a P variance value of 120 ms2 separated patients from controls with a sensitivity of 88%, 83%, and 80%, respectively and a specificity of 75%, 85%, and 74%, respectively. The reproducibility of P variance was higher compared to P dispersion and P maximum. Finally, the PC-based method significantly increased accuracy and reproducibility of P wave measurements. Thus, the variance of P wave duration could be a useful ECG marker for the prediction of paroxysmal idiopathic AF and the use of PC-based methods may enhance the accurate measuring of P wave duration on the ECG.