Non-invasive cardiac mapping for non-response in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is an effective intervention in selected patients with moderate-to-severe heart failure with reduced ejection fraction and abnormal left ventricular activation time. The non-response rate of approximately 30% has remained nearly unchanged since this therapy was introduced 25 years ago. While intracardiac mapping is widely used for diagnosis and guidance of therapy in patients with tachyarrhythmia, its application in characterization of the electrical substrate to elucidate the mechanisms involved in CRT response remain anecdotal. In the present review, we describe the traditional determinants of CRT response before presenting novel non-invasive techniques used for CRT optimization. We discuss efforts to identify the target electrical substrate to guide the deployment of pacing electrodes during the operative procedure. Non-invasive body surface mapping technologies such as ECG imaging or ECG belt enables prediction of acute and chronic CRT response. While electrical dyssynchrony parameters provide high predictive accuracy for CRT response when obtained during intrinsic conduction, their predictive value is less when acquired during CRT or LV-pacing.

Key messages

• Classic predictors of CRT response are female gender, NYHA class ≤ III, left ventricular ejection fraction ≥25%, QRS duration ≥150 ms and estimated glomerular filtration rate ≥60 mL/min.
• ECG-imaging is a comprehensive non-invasive mapping system which allows to express the amount of electrical asynchrony of a CRT candidate.
• Non-invasive body surface mapping technologies enables excellent prediction of acute and chronic CRT response before implantation.
• When performed during CRT or LV-pacing, the added value of these mapping systems remains unclear.

     

Mixed venous blood gas sampling is not influenced by the speed of withdrawal in cardiac surgery patients

Objective To determine whether mixed venous blood gas sampling obtained by pulmonary artery catheter (PAC) is influenced by the speed of withdrawal.Design Prospective, observational study.Setting Surgical intensive care unit at a university hospital.Subjects Twenty-five patients in the early postoperative period of cardiac surgery.Measurements and main results After verification of the adequate position of the PAC, measurements of mixed venous blood gas oxygen saturation, oxygen partial pressure (PO₂), carbon dioxide partial pressure (PCO₂), pH and bicarbonates were obtained at two different rates of withdrawal. A slow sampling was taken at a mean speed of 3 ml/min and a fast sampling at 18 ml/min for each patient. The mean difference in venous oxygen saturation between slow and fast samplings was -0.18±1.3%, venous PO₂: –0.2±1.3 mmHg, venous PCO₂: 0.1±0.9 mmHg, venous pH: 0±0.03, venous bicarbonates: 0.03±0.5 mmol/l.Conclusion Using the Bland & Altman method, we showed a satisfactory agreement between slow and fast mixed venous blood gas sampling techniques when measuring PO₂, oxygen saturation, PCO₂, pH and bicarbonates though a PAC.Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134.004.2392-4This study was supported by the Plan de pratique des anesthésiologistes de lInstitut de Cardiologie de Montréal.     

Pacemaker endocarditis: clinical features and management of 60 consecutive cases

BACKGROUND: The incidence of endocarditis related to pacemakers is increasing, while the diagnosis and management remain difficult. The objective of this study was to evaluate the clinical features and management of endocarditis after implantation of pacemakers (PM) or cardioverter defibrillators (ICD). METHODS: We analyzed the hospital course of 60 consecutive patients (48 men, mean age 68 +/- 12 years) admitted to our center for PM (n = 59) or ICD (n = 1) endocarditis between 1998 and 2004. RESULTS: Fever (78%), asthenia (65%), and local symptoms (35%) were common. Positive cultures were obtained in 53 cases (Staphylococcus 89%). Sixteen patients (27%) had pulmonary embolism. Vegetations (mean size 15.2 +/- 8 mm, range 5 to 35 mm) were found in 54 cases (90%), with transthoracic echocardiography in 26 cases (43%), and transesophageal echocardiography (TEE) in 50 cases (89% of the 56 patients who had TEE). Devices were removed surgically (n = 20) or percutaneously (n = 37). In the surgical group, vegetations were larger (17.9 +/- 7 mm vs 13.2 +/- 7 mm, P = 0.01). After removal, 42 patients (70%) had a new PM. Mortality factors (6 deaths - follow up 3.4 +/- 2 years) were the number of vegetations and absence of extraction of the device (P < 0.02). Clinical features and management of the 37 patients with early onset endocarditis (within 1 year after implantation) did not differ from those with late onset. CONCLUSIONS: PM endocarditis was essentially staphylococcal. TEE was required for the diagnosis of vegetations. Complete removal of the device is required and associated with a favorable outcome.     

Measuring Pavlovian appetitive conditioning in humans with the postauricular reflex

Despite its evolutionary and clinical significance, appetitive conditioning has been rarely investigated in humans. It has been proposed that this discrepancy might stem from the difficulty in finding suitable appetitive stimuli that elicit strong physiological responses. However, this might also be due to a possible lack of sensitivity of the psychophysiological measures commonly used to index human appetitive conditioning. Here, we investigated whether the postauricular reflex—a vestigial muscle microreflex that is potentiated by pleasant stimuli relative to neutral and unpleasant stimuli—may provide a valid psychophysiological indicator of appetitive conditioning in humans. To this end, we used a delay differential appetitive conditioning procedure, in which a neutral stimulus was contingently paired with a pleasant odor (CS+), while another neutral stimulus was not associated with any odor (CS?). We measured the postauricular reflex, the startle eyeblink reflex, and skin conductance response (SCR) as learning indices. Taken together, our results indicate that the postauricular reflex was potentiated in response to the CS+ compared with the CS?, whereas this potentiation extinguished when the pleasant odor was no longer delivered. In contrast, we found no evidence for startle eyeblink reflex attenuation in response to the CS+ relative to the CS?, and no effect of appetitive conditioning was observed on SCR. These findings suggest that the postauricular reflex is a sensitive measure of human appetitive conditioning and constitutes a valuable tool for further shedding light on the basic mechanisms underlying emotional learning in humans.     

The aging anesthesiologist: a narrative review and suggested strategies

Purpose

To address an aging anesthesia workforce, we review the relevant changes and implications associated with age in order to stimulate discussion at the individual, local, and national levels regarding appropriate changes in practice aimed at protecting patient safety.

Principal findings

In a 2013 survey of Canadian Anesthesiologists, 22% were aged 55-64 yr, 7% were aged 65-74 yr, and 3% were older than 74 yr. Clinical abilities decline with age, making older anesthesiologists more likely than their younger colleagues to be associated with adverse patient events. Anesthesiologists older than 65 yr in Ontario, Quebec, and British Columbia had 50% more cases involving litigation and almost twice the number of cases involving severe patient injury compared with anesthesiologists younger than 51 yr of age. In the absence of overt deterioration in skills, decisions about reducing activities and retirement are left largely to individuals despite their limited ability to self-assess competence. This state of affairs may contribute to the increased incidence of adverse events and poor patient outcomes.

Conclusions

Provincial regulatory bodies have peer assessment programs to evaluate physicians at random, following a complaint, and at certain ages, but all have limitations. Simulation has been used widely for training and assessment in the aviation industry as well as in automobile driving exams. Simulation can assess crisis recognition and management, which is crucial in anesthesiology and not well assessed by other methods, and could assist elderly anesthesiologists during the pre-retirement phase of their careers. A standardized schedule for winding down would have advantages for physicians, their department, and their patients. A suggested schedule might include no further on-call duties for those aged 60 yr and older, no further high-acuity cases for those aged 65 yr and older, and retirement from operating room (OR) clinical practice (with possible continuation of non-OR clinical or other non-clinical activities, if desired) at age 70 yr. These timelines could be extended with satisfactory performance in annual simulation sessions involving assessment and practice in crisis management.     

The effect of a period of intense exercise on the marker approach to detect growth hormone doping in sports

The major objective of this study was to investigate the effects of several days of intense exercise on the growth hormone marker approach to detect doping with human growth hormone (hGH). In addition we investigated the effect of changes in plasma volume on the test. Fifteen male athletes performed a simulated nine‐day cycling stage race. Blood samples were collected twice daily over a period of 15 days (stage race + three days before and after). Plasma volumes were estimated by the optimized CO Rebreathing method. IGF‐1 and P‐III‐NP were analyzed by Siemens Immulite and Cisbio Assays, respectively. All measured GH 2000 scores were far below the published decision limits for an adverse analytical finding. The period of exercise did not increase the GH‐scores; however the accompanying effect of the increase in Plasma Volume yielded in essentially lower GH‐scores. We could demonstrate that a period of heavy, long‐term exercise with changes in plasma volume does not interfere with the decision limits for an adverse analytical finding. Copyright © 2014 John Wiley & Sons, Ltd.     

Xenobiotic metabolism induction and bulky DNA adducts generated by particulate matter pollution in BEAS‐2B cell line: geographical and seasonal influence

Airborne particulate matter (PM) toxicity is of growing interest as diesel exhaust particles have been classified as carcinogenic to humans. However, PM is a mixture of chemicals, and respective contribution of organic and inorganic fractions to PM toxicity remains unclear. Thus, we analysed the link between chemical composition of PM samples and bulky DNA adduct formation supported by CYP1A1 and 1B1 genes induction and catalytic activities. We used six native PM samples, collected in industrial, rural or urban areas, either during the summer or winter, and carried out our experiments on the human bronchial epithelial cell line BEAS‐2B. Cell exposure to PM resulted in CYP1A1 and CYP1B1 genes induction. This was followed by an increase in EROD activity, leading to bulky DNA adduct formation in exposed cells. Bulky DNA adduct intensity was associated to global EROD activity, but this activity was poorly correlated with CYPs mRNA levels. However, EROD activity was correlated with both metal and polycyclic aromatic hydrocarbon (PAH) content. Finally, principal components analysis revealed three clusters for PM chemicals, and suggested synergistic effects of metals and PAHs on bulky DNA adduct levels. This study showed the ability of PM samples from various origins to generate bulky DNA adducts in BEAS‐2B cells. This formation was promoted by increased expression and activity of CYPs involved in PAHs activation into reactive metabolites. However, our data highlight that bulky DNA adduct formation is only partly explained by PM content in PAHs, and suggest that inorganic compounds, such as iron, may promote bulky DNA adduct formation by supporting CYP activity. Copyright © 2013 John Wiley & Sons, Ltd.     

Heightened D3 Dopamine Receptor Levels in Cocaine Dependence and Contributions to the Addiction Behavioral Phenotype: A Positron Emission Tomography Study with [11C]-(+)-PHNO

The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D₂ receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D₃ receptor system has recently attracted considerable clinical interest, and D₃ antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D₃ receptor system in CD, using the positron emission tomography (PET) radiotracer [¹¹C]-(+)-PHNO. Fifteen CD subjects (many actively using, but all abstinent 7–240 days on scan day) and fifteen matched healthy control (HC) subjects completed two PET scans: one with [¹¹C]-(+)-PHNO to assess D₃ receptor binding (BP_ND; calculated regionally using the simplified reference tissue model), and for comparison, a second scan with [¹¹C]raclopride to assess D_2/3 binding. CD subjects also completed a behavioral battery to characterize the addiction behavioral phenotype. CD subjects showed higher [¹¹C]-(+)-PHNO BP_ND than HC in the substantia nigra, which correlated with behavioral impulsiveness and risky decision making. In contrast, [¹¹C]raclopride BP_ND was lower across the striatum in CD, consistent with previous literature in ⩾2 week abstinence. The data suggest that in contrast to a D₂ deficiency, CD individuals may have heightened D₃ receptor levels, which could contribute to addiction-relevant traits. D₃ upregulation is emerging as a biomarker in preclinical models of addiction, and human PET studies of this receptor system can help guide novel pharmacological strategies for treatment.     

Stress-Induced Dopamine Response in Subjects at Clinical High Risk for Schizophrenia with and without Concurrent Cannabis Use

Research on the environmental risk factors for schizophrenia has focused on either psychosocial stress or drug exposure, with limited investigation of their interaction. A heightened dopaminergic stress response in patients with schizophrenia and individuals at clinical high risk (CHR) supports the dopaminergic sensitization hypothesis. Cannabis is believed to contribute to the development of schizophrenia, possibly through a cross-sensitization with stress. Twelve CHR and 12 cannabis-using CHR (CHR-CU, 11 dependent) subjects underwent [¹¹C]-(+)-PHNO positron emission tomography scans, while performing a Sensorimotor Control Task (SMCT) and a stress condition (Montreal Imaging Stress task). The simplified reference tissue model was used to obtain binding potential relative to non-displaceable binding (BP_ND) in the whole striatum, its functional subdivisions (limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST)), globus pallidus (GP), and substantia nigra (SN). Changes in BP_ND, reflecting alterations in synaptic dopamine (DA) levels, were tested with analysis of variance. SMCT BP_ND was not significantly different between groups in any brain region (p>0.21). Although stress elicited a significant reduction in BP_ND in the CHR group, CHR-CU group exhibited an increase in BP_ND. Stress-induced changes in regional BP_ND between CHR-CU and CHR were significantly different in AST (p<0.001), LST (p=0.007), SMST (p=0.002), SN (p=0.021), and whole striatum (p=0.001), with trend level in the GP (p=0.099). All subjects experienced an increase in positive (attenuated) psychotic symptoms (p=0.001) following the stress task. Our results suggest altered DA stress reactivity in CHR subjects who concurrently use cannabis, as compared with CHR subjects. Our finding does not support the cross-sensitization hypothesis, which posits greater dopaminergic reactivity to stress in CHR cannabis users, but adds to the growing body of literature showing reduced DA (stress) response in addiction.     

Quantitative imaging of neuroinflammation in human white matter: A positron emission tomography study with translocator protein 18 kDa radioligand, [18F]‐FEPPA

The ability to quantify translocator protein 18 kDa (TSPO) in white matter (WM) is important to understand the role of neuroinflammation in neurological disorders with WM involvement. This article aims to extend the utility of TSPO imaging in WM using a second‐generation radioligand, [¹⁸F]‐FEPPA, and high‐resolution research tomograph (HRRT) positron emission tomography (PET) camera system. Four WM regions of interests (WM‐ROI), relevant to the study of aging and neuroinflammatory diseases, were examined. The corpus callosum, cingulum bundle, superior longitudinal fasciculus, and posterior limb of internal capsule were delineated automatically onto subject's T₁‐weighted magnetic resonance image using a diffusion tensor imaging‐based WM template. The TSPO polymorphism (rs6971) stratified individuals to three genetic groups: high‐affinity binders (HAB), mixed‐affinity binders (MAB), and low‐affinity binders. [¹⁸F]‐FEPPA PET scans were acquired on 32 healthy subjects and analyzed using a full kinetic compartment analysis. The two‐tissue compartment model showed moderate identifiability (coefficient of variation 15–19%) for [¹⁸F]‐FEPPA total volume distribution (V_T) in WM‐ROIs. Noise affects V_T variability, although its effect on bias was small (6%). In a worst‐case scenario, ≤6% of simulated data did not fit reliably. A simulation of increased TSPO density exposed minimal effect on variability and identifiability of [¹⁸F]‐FEPPA V_T in WM‐ROIs. We found no association between age and [¹⁸F]‐FEPPA V_T in WM‐ROIs. The V_T values were 15% higher in HAB than in MAB, although the difference was not statistically significant. This study provides evidence for the utility and limitations of [¹⁸F]‐FEPPA PET to measure TSPO expression in WM. Synapse 68:536–547, 2014 . © 2014 Wiley Periodicals, Inc.