Bradycardia and atrial fibrillation in patients with stable coronary artery disease treated with ivabradine: an analysis from the SIGNIFY study

Aim: The aim of this study was to determine the impact of emergent bradycardia and atrial fibrillation (AF) on cardiovascular outcomes in 19 083 patients with stable coronary artery disease (CAD) receiving ivabradine or placebo (SIGNIFY, Study assessInG the morbidity–mortality beNefits of the If inhibitor ivabradine in patients with coronarY artery disease). Methods and results: Emergent bradycardia (resting heart rate <50 b.p.m. on 12-lead electrocardiogram) with ivabradine was reported in 3572 patients (37.4%) overall, and in 2242 (37.2%) patients with Canadian Cardiovascular Society (CCS) class ≥2 angina. There was no difference in outcomes over the course of the study in ivabradine-treated patients with and without emergent bradycardia in the whole population (2.5 vs. 2.9% per year, respectively, for primary composite endpoint of cardiovascular death or non-fatal myocardial infarction) or in the angina subgroup (2.5 vs. 3.2% per year). Neither was there an increase in the rate of primary endpoint after emergent bradycardia was recorded compared with those without emergent bradycardia. There were 754 cases of emergent AF on treatment (2.2% per year ivabradine vs. 1.5% per year placebo) and 469 in the patients with angina (2.2 vs. 1.5% per year). While outcomes occurred more frequently in patients in whom emergent AF had been recorded, there was no treatment–placebo difference in outcomes, including stroke, and no difference in treatment effect in patients with limiting angina. Conclusion: Both in the overall population as well as in the angina subset, bradycardia was common in ivabradine-treated patients, but did not appear to impact outcomes. Emergent AF was relatively rare and did not appear to have an impact on outcomes relative to placebo

Modulation of Neurally Mediated Vasodepression and Bradycardia by Electroacupuncture through Opioids in Nucleus Tractus Solitarius.

Stimulation of vagal afferent endings with intravenous phenylbiguanide (PBG) causes both bradycardia and vasodepression, simulating neurally mediated syncope. Activation of µ-opioid receptors in the nucleus tractus solitarius (NTS) increases blood pressure. Electroacupuncture (EA) stimulation of somatosensory nerves underneath acupoints P5-6, ST36-37, LI6-7 or G37-39 selectively but differentially modulates sympathoexcitatory responses. We therefore hypothesized that EA-stimulation at P5-6 or ST36-37, but not LI6-7 or G37-39 acupoints, inhibits the bradycardia and vasodepression through a µ-opioid receptor mechanism in the NTS. We observed that stimulation at acupoints P5-6 and ST36-37 overlying the deep somatosensory nerves and LI6-7 and G37-39 overlying cutaneous nerves differentially evoked NTS neural activity in anesthetized and ventilated animals. Thirty-min of EA-stimulation at P5-6 or ST36-37 reduced the depressor and bradycardia responses to PBG while EA at LI6-7 or G37-39 did not. Congruent with the hemodynamic responses, EA at P5-6 and ST36-37, but not at LI6-7 and G37-39, reduced vagally evoked activity of cardiovascular NTS cells. Finally, opioid receptor blockade in the NTS with naloxone or a specific μ-receptor antagonist reversed P5-6 EA-inhibition of the depressor, bradycardia and vagally evoked NTS activity. These data suggest that point specific EA stimulation inhibits PBG-induced vasodepression and bradycardia responses through a μ-opioid mechanism in the NTS

Apnea, bradycardia and desaturation spells in premature infants: impact of a protocol for the duration of 'spell-free' observation on interprovider variability and readmission rates.

ObjectiveTo study the impact of implementing a protocol to standardize the duration of observation in preterm infants with apnea/bradycardia/desaturation spells before hospital discharge on length of stay (LOS) and readmission rates.Study designA protocol to standardize the duration of in-hospital observation for preterm infants with apnea, bradycardia and desaturation spells who were otherwise ready for discharge was implemented in December 2013. We evaluated the impact of this protocol on the LOS and readmission rates of very low birth weight infants (VLBW). Data on readmission for apnea and an apparent life-threatening event (ALTE) within 30 days of discharge were collected. The pre-implementation epoch (2011 to 2013) was compared to the post-implementation period (2014 to 2016).ResultsThere were 426 and 368 VLBW discharges before and after initiation of the protocol during 2011 to 2013 and 2014 to 2016, respectively. The LOS did not change with protocol implementation (66±42 vs 64±42 days before and after implementation of the protocol, respectively). Interprovider variability on the duration of observation for apneic spells (F-8.8, P=0.04) and bradycardia spells (F-17.4, P<0.001) decreased after implementation of the protocol. The readmission rate for apnea/ALTE after the protocol decreased from 12.1 to 3.4% (P=0.01).ConclusionImplementing an institutional protocol for VLBW infants to determine the duration of apnea/bradycardia/ desaturation spell-free observation period as recommended by the American Academy of Pediatrics clinical report did not prolong the LOS but effectively reduced interprovider variability and readmission rates

Skin blood flow changes during apneic spells in preterm infants

Changes in skin blood flow during apneic spells were determined in 18 preterm infants using a diode laser Doppler flow meter without light conducting fibres. Heart rate, nasal air flow, impedance pneumography, skin and incubator temperature and laser Doppler skin blood flow were recorded simultaneously in each infant. During 212 apneic spells with a duration of 11.6 ± 7.5 s (mean ± S.D.) (range 6.0–48.0 s), the laser Doppler skin blood flow was measured. In all children except one, the majority of the apneic spells was associated with a decrease in skin blood flow. During 155 apneic spells (73%) skin blood flow decreased significantly P < 0.025), the maximum decrease being 16.7 ± 14.8%, 28.5 ± 23.9% and 18.9 ± 16.1% (mean ± S.D.) for central, obstructive and mixed apneic spells, respectively. The decrease in skin blood flow started immediately after the beginning of apneic spells in 71%, the rest started with a mean delay of 3.4 s (range 0.1–7.0 s). No relation was found between the decrease in skin blood flow and the duration of the apneic spells. Thirty-four percent of the apneic spells were accompanied by bradycardia. In apneic spells accompanied by bradycardia the decrease in skin blood flow was not related to the fall in heart rate

Detection of Salinity by the Lobster, Homarus americanus

Changes in the heart rates of lobsters (Homarus americanus) were used as an indicator that the animals were capable of sensing a reduction in the salinity of the ambient seawater. The typical response to a gradual (1 to 2 ppt/min) reduction in salinity consisted of a rapid increase in heart rate at a mean threshold of 26.6 ± 0.7 ppt, followed by a reduction in heart rate when the salinity reached 22.1 ± 0.5 ppt. Animals with lesioned cardioregulatory nerves did not exhibit a cardiac response to changes in salinity. A cardiac response was elicited from lobsters exposed to isotonic chloride-free salines but not to isotonic sodium-, magnesium- or calcium-free salines. There was little change in the blood osmolarity of lobsters when bradycardia occurred, suggesting that the receptors involved are external. Furthermore, lobsters without antennae, antennules, or legs showed typical cardiac responses to low salinity, indicating the receptors are not located in these areas. Lobsters exposed to reductions in the salinity of the ambient seawater while both branchial chambers were perfused with full-strength seawater did not display a cardiac response until the external salinity reached 21.6 ± 1.8 ppt. In contrast, when their branchial chambers were exposed to reductions in salinity while the external salinity was maintained at normal levels, changes in heart rate were rapidly elicited in response to very small reductions in salinity (down to 29.5 ± 0.9 ppt in the branchial chamber and 31.5 ± 0.3 ppt externally). We conclude that the primary receptors responsible for detecting reductions in salinity in H. americanus are located within or near the branchial chambers and are primarily sensitive to chloride ions

Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery

Selenium-binding protein 1 (SELENBP1) is an intracellular protein that has been detected in the circulation in response to myocardial infarction. Hypoxia and cardiac surgery affect selenoprotein expression and selenium (Se) status. For this reason, we decided to analyze circulating SELENBP1 concentrations in patients (n = 75) necessitating cardioplegia and a cardiopulmonary bypass (CPB) during the course of the cardiac surgery. Serum samples were collected at seven time-points spanning the full surgical process. SELENBP1 was quantified by a highly sensitive newly developed immunological assay. Serum concentrations of SELENBP1 increased markedly during the intervention and showed a positive association with the duration of ischemia (ρ = 0.6, p < 0.0001). Elevated serum SELENBP1 concentrations at 1 h after arrival at the intensive care unit (post-surgery) were predictive to identify patients at risk of adverse outcome (death, bradycardia or cerebral ischemia, "endpoint 1"; OR 29.9, CI 3.3-268.8, p = 0.00027). Circulating SELENBP1 during intervention (2 min after reperfusion or 15 min after weaning from the CPB) correlated positively with an established marker of myocardial infarction (CK-MB) measured after the intervention (each with ρ = 0.5, p < 0.0001). We concluded that serum concentrations of SELENBP1 were strongly associated with cardiac arrest and the duration of myocardial ischemia already early during surgery, thereby constituting a novel and promising quantitative marker for myocardial hypoxia, with a high potential to improve diagnostics and prediction in combination with the established clinical parameters

Association Rules Mining Based Clinical Observations

Healthcare institutes enrich the repository of patients' disease related information in an increasing manner which could have been more useful by carrying out relational analysis. Data mining algorithms are proven to be quite useful in exploring useful correlations from larger data repositories. In this paper we have implemented Association Rules mining based a novel idea for finding co-occurrences of diseases carried by a patient using the healthcare repository. We have developed a system-prototype for Clinical State Correlation Prediction (CSCP) which extracts data from patients' healthcare database, transforms the OLTP data into a Data Warehouse by generating association rules. The CSCP system helps reveal relations among the diseases. The CSCP system predicts the correlation(s) among primary disease (the disease for which the patient visits the doctor) and secondary disease/s (which is/are other associated disease/s carried by the same patient having the primary disease).Comment: 5 pages, MEDINFO 2010, C. Safran et al. (Eds.), IOS Pres