Distinct impacts of heart rate and right atrial‐pacing on left atrial mechanical activation and optimal AV delay in CRT

1 Background

Controversy exists regarding how atrial activation mode and heart rate affect optimal atrioventricular (AV) delay in cardiac resynchronization therapy. We studied these questions using high‐reproducibility hemodynamic and echocardiographic measurements.

2 Methods

Twenty patients were hemodynamically optimized using noninvasive beat‐to‐beat blood pressure at rest (62 ± 11 beats/min), during exercise (80 ± 6 beats/min), and at three atrially paced rates: 5, 25, and 45 beats/min above rest, denoted as A_paced,r+5, A_paced,r+25, and A_paced,r+45, respectively. Left atrial myocardial motion and transmitral flow were timed echocardiographically.

3 Results

During atrial sensing, raising heart rate shortened optimal AV delay by 25 ± 6 ms (P < 0.001). During atrial pacing, raising heart rate from A_paced,r+5 to A_paced,r+25 shortened it by 16 ± 6 ms; A_paced,r+45 shortened it 17 ± 6 ms further (P < 0.001). In comparison to atrial‐sensed activation, atrial pacing lengthened optimal AV delay by 76 ± 6 ms (P < 0.0001) at rest, and at ～20 beats/min faster, by 85 ± 7 ms (P < 0.0001), 9 ± 4 ms more (P  =  0.017). Mechanically, atrial pacing delayed left atrial contraction by 63 ± 5 ms at rest and by 73 ± 5 ms (i.e., by 10 ± 5 ms more, P < 0.05) at ～20 beats/min faster. Raising atrial rate by exercise advanced left atrial contraction by 7 ± 2 ms (P  =  0.001). Raising it by atrial pacing did not (P  =  0.2).

4 Conclusions

Hemodynamic optimal AV delay shortens with elevation of heart rate. It lengthens on switching from atrial‐sensed to atrial‐paced at the same rate, and echocardiography shows this sensed‐paced difference in optima results from a sensed‐paced difference in atrial electromechanical delay. The reason for the widening of the sensed‐paced difference in AV optimum may be physiological stimuli (e.g., adrenergic drive) advancing left atrial contraction during exercise but not with fast atrial pacing.     

French pre-hospital trauma triage criteria:Does the “prehospital resuscitation” criterion provide additional benefit in triage?

AIM: To evaluate the performance of the specific French Vittel “Pre-Hospital (PH) resuscitation” criteria in selecting polytrauma patients during the pre-hospital stage and its potential to increase the positive predictive value (PPV) of pre-hospital trauma triage.METHODS: This was a monocentric prospective cohort study of injured adults transported by emergency medical service to a trauma center. Patients who met any of the field trauma triage criteria were considered “triage positive”. Hospital data was statistically linked to pre-hospital records. The primary outcome of defining a “major trauma patient” was Injury Severity Score (ISS) > 16.RESULTS: There were a total of 200 injured patients evaluated over a 2 years period who met at least 1 triage criterion. The number of false positives was 64 patients (ISS < 16). The PPV was 68%. The sensitivity and the negative predictive value could not be evaluated in this study since it only included patients with positive Vittel criteria. The criterion of “PH resuscitation” was present for 64 patients (32%), but 10 of them had an ISS < 16. This was statistically significant in correlation with the severity of the trauma in univariate analysis (OR = 7.2; P = 0.005; 95%CI: 1.6-31.6). However, despite this correlation the overall PPV was not significantly increased by the use of the criterion “PH resuscitation” (68% vs 67.8%).CONCLUSION: The criterion of “pre-hospital resuscitation” was statistically significant with the severity of the trauma, but did not increase the PPV. The use of “pre-hospital resuscitation” criterion could be re-considered if these results are confirmed by larger studies.     

Glucoregulation and hormonal changes during prolonged exercise in boys and girls

A group of 17 children, 8.5–11 years old, performed a 60-min cycle exercise at 60% of maximal oxygen uptake (VO_2max) 2 h after a standardized breakfast. They were 10 young boys (pubertal stage =1) and 7 young girls (pubertal stage 2) of similarVO_2max (respective values were 48.5 ml min^–1 kg^–1, SEM 1.8; 42.1 ml min^–1 kg^–1, SEM 2.4). Blood samples of 5 ml were withdrawn by heparinized catheter, the subjects being in a supine position, 30 min before the test, then after 0, 15, 30 and 60 min of exercise and following 30 min recovery. Haematocrit was immediately measured. Thereafter plasma was analysed for glucose, non-esterified fatty acid, glycerol, catecholamine (noradrenaline, adrenaline), insulin and glucagon concentrations. This study showed two main results. First, the onset of exercise induced a significant glucose decrease (of about 11,4%) in all the children. Secondly, both the glycaemic and the hormonal responses were obviously different according to the sex. In boys only, the initial glucose drop was significantly correlated to the pre-exercise insulin values. Whatever the time, the glycaemic levels and the catecholamine responses were lower in girls than in boys, whereas the insulin values remained higher. However, none of these two hormonal parameters seemed to be really responsible for the lower glucose values in girls. On the one hand, the great individual variability of noradrenaline and adrenaline and differences in their relative intensity at the end of the exercise between boys and girls might contribute to the lower catecholamine levels in girls. On the other hand, the lack of a significant relationship in girls between the glucose decrease after exercise and the pre-exercise insulin values might be explained by a relative insulin insensitivity concomitant with the earlier growth spurt in girls, as demonstrated in subjects at rest by other authors. Finally the mechanisms of all these gender differences remain to be clarified and might be accounted for by a different maturation level in boys and girls.     

The atrioventricular delay of cardiac resynchronization can be optimized hemodynamically during exercise and predicted from resting measurements

BACKGROUND: Atrioventricular (AV) optimization of cardiac resynchronization therapy (CRT) is typically calculated at rest. However, patients often become symptomatic during exercise. OBJECTIVE: In this study, we use acute noninvasive hemodynamics to optimize the AV delay of CRT during exercise and investigate whether this exercise optimum can be predicted from a three-phase resting model. METHODS: In 20 patients with CRT, we adjusted the sensed AV delay while the patient exercised on a treadmill up to a heart rate of 100 bpm to identify the hemodynamically optimal value. Separately, at rest, by pacing with three different configurations and calculating the sensed-paced difference, we calculated an "expected" value for the exercise optimum. RESULTS: It was possible to perform AV delay optimization while a patient exercised. The resting three-phase model correlated well with the actual exercise optimal AV delay (r = 0.85, mean difference +/- standard deviation [SD] = 3.7 +/- 17 ms). Simply using measurements made at rest during atrial-sensed pacing showed a poorer correlation with exercise (r = 0.64, mean difference +/- SD = 2.2 +/- 24 ms). The three-phase resting model allows improved exercise hemodynamics to be achieved. Programming according to the three-phase resting model yields an exercise blood pressure of only 0.5 mmHg (+/-1.4 mmHg; P = NS) less than the true exercise optimum, whereas programming the resting sensed optimum yields an exercise blood pressure of 1.4 mmHg (+/-2.2 mmHg, P = .02) less than the true optimum. CONCLUSIONS: Using acute noninvasive hemodynamics and a protocol of alternations, it is possible to optimize the AV delay of cardiac resynchronization devices even while a patient exercises. In clinical practice, the exercise optimum AV delay could be determined from three phases of resting measurements, without performing exercise.     

Gastrointestinale Tumoren

Paraneoplastic syndromes, as syndromes associated with malignancy, can present unrelated to tumor invasion or metastases. They can occur with varying clinical appearance and are often indistinguishable from idiopathic rheumatic symptoms. Some musculoskeletal disorders are more associated with malignancies. The therapy of rheumatic syndromes can itself have an effect on the tumorigenic process. The clinical severity of paraneoplastic rheumatic symptoms can in many cases aid in the assessment of tumor activity and the response to therapy. While generally an extensive search for occult malignancies in every older rheumatoid patient in cases with no indications of malignancy is not advisable, knowledge of rheumatic symptoms associated with malignancies aids in the important early detection of tumors, while avoiding unnecessary examinations.     

Mycophenolate mofetil versus azathioprine in patients with chronic active ulcerative colitis: a 12-month pilot study

OBJECTIVE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology frequently requiring long-term therapy for control of symptoms and prevention of relapse. Azathioprine (AZA) has been shown to be effective and safe in the treatment of chronic active UC. However, the alternatives to treatment with AZA are limited. Our aim was to compare the efficacy and safety of treatment with mycophenolate mofetil (MMF)/prednisolone versus standard immunosuppressive treatment with azathioprine (AZA)/prednisolone in patients with chronic active UC. METHODS: The study was designed as an open comparison of MMF versus AZA. Twenty-four patients with active UC (Rachmilewitz score > or =6 points) were randomly assigned to the MMF (20 mg/kg)/prednisolone or AZA (2 mg/kg)/prednisolone group. The initial prednisolone dosage was 50 mg and was tapered according to a standard protocol. Treatment was scheduled for 1 yr. RESULTS: The rates of remission were higher in the AZA/prednisolone group (n = 12) than in the MMF/prednisolone group (n = 12) throughout the study. Remission rates were 92% versus 67% after 4 wk, 92% versus 67% after 3 months, 92% versus 67% after 6 months, 83% versus 78% after 9 months, and 100% versus 88% after 1 yr. The number of patients not requiring steroids was higher in the AZA/prednisolone group than in the MMF/prednisolone group. Moreover, in the AZA/prednisolone group no severe adverse events were recorded, whereas in the MMF/prednisolone group two severe adverse events were observed: one patient discontinued MMF after 6 months because of recurrent upper airway infections, and one patient exhibited a bacterial meningitis after 9 months. CONCLUSIONS: Treatment with AZA/prednisolone appears to be more effective and safe compared to MMF/prednisolone in patients with chronic active UC. MMF might be an alternative treatment for patients with contraindications to AZA. To further evaluate the effects of MMF in active UC, a placebo-controlled double-blinded study appears warranted.     

Anticoagulation for cardioversion of atrial fibrillation

The cardioversion of chronic atrial fibrillation to sinus rhythm carries a thromboembolic risk of 1.5-6%. These events occasionally occur at the time of cardioversion, but more often happen hours or days later. These strokes and other embolic events may occur even where atrial thrombus has been excluded before cardioversion and it has become apparent that, although atrial electrical activity may be restored by cardioversion, normal mechanical atrial function may take longer to recover. Numerous studies have addressed the role of anticoagulation following cardioversion in patients with atrial fibrillation, however, the mechanism of embolic complications as well as the justification of a standard anticoagulation therapy are not fully established. In this review we will try to present an overview of the mechanisms of thrombosis following cardioversion and give an insight into current anticoagulation strategies.     

Effect of lupines, a protein-rich legume, on iron absorption

The absorption of iron from lupines, a protein-rich legume, was assessed in 35 parous Indian women. Iron bioavailability was shown to be as low for lupines as soybeans (geometric mean absorptions 0.9 and 1.7 per cent respectively, P less than 0.005). The addition of 30 mg of ascorbic acid moderately improved the geometric mean iron absorption from 1.0 to 5.3 per cent (P less than 0.0001), and 60 mg ascorbic acid from 0.7 to 6.9 per cent (P less than 0.0001). The phytate and polyphenol content of lupines was negligible. The demonstration of poor iron bioavailability from a legume of otherwise rich nutritional potential has important implications in nutritional planning programmes for developing countries.