Left Ventricular Dysfunction Caused by Unrecognized Surgical AV block in a Patient with a Manifest Right Free Wall Accessory Pathway

A 24-year-old male with Wolff-Parkinson-White syndrome developed systolic cardiomyopathy and severe heart failure following membranous ventricular septal defect repair and tricuspid valve replacement. Following successful catheter ablation of a right anterolateral accessory pathway (AP), complete AV block with junctional escape rhythm was noted. Patient subsequently underwent implantation of a biventricular ICD. Heart failure symptoms significantly improved soon after and left ventricular systolic function normalized 3 months post-procedure. In this case, surgically acquired AV block likely explains development of postoperative cardiomyopathy by facilitating ventricular activation solely via the AP and thereby increasing the degree of ventricular dyssynchrony.     

Differences in scapular kinematics and scapulohumeral rhythm during elevation and lowering of the arm between typical children and healthy adults

Scapular kinematics in healthy adults is well described in the literature but little is known on typical children. This study aimed to compare the three-dimensional (3-D) scapular kinematics and scapulohumeral rhythm during the elevation and lowering of the arm in the scapular plane in typical children and healthy adults. Twenty-six healthy adults (35.34 ± 11.65 years, 1.70 ± 0.10 m, 70.00 ± 12.30 kg) and 33 typical children (9.12 ± 1.51 years, 1.40 ± 0.10 m, 35.40 ± 10.45 kg) participated in this study. 3-D scapular kinematics were obtained using an electromagnetic tracking device. The subjects were asked to elevate and lower their arm in the scapular plane. Children showed less scapular protraction compared to adults at 120° during arm elevation, more anterior tilt than adults in the elevation and also at 60°, 90° and 120° during lowering of the arm. Children also showed higher scapulohumeral rhythm during lowering of the arm compared to adults from 90° to 60°. It was also found a low to little correlation between scapular position and age. The study showed small but significant differences in scapular kinematics and scapulohumeral rhythm between children and adults. These results can help clinicians to improve diagnosis and treatment protocols directed to children with dysfunction, as reference values on scapular kinematics in healthy children are also provided in this study.     

A linear ablating system in the left and right atrium: feasibility, catheter performance and clinical results

IntroductionWe describe the use of a ablating system to compartmentalise and regionally isolate the atria in paroxysmal and persistent atrial fibrillation (AF).Methods40 patients were studied, 25 paroxysmal AF and 14 persistent AF. One patient enrolled was later found to be in left atrial flutter and was excluded. The Cardima Revelation® TX catheter system with Intellitemp® Radiofrequency (RF) energy control device and a Medtronic Atakar® RF generator were used to place wide area circumferential ablations to achieve conduction block into the left and right sided pulmonary veins. Roof lines and mitral isthmus lines were also performed. In patients with persistent AF and in repeat procedures, right atrial compartmentalisation was performed with an anterior superior vena cava (SVC) to inferior vena cava (IVC) line and a septal SVC to IVC line.ResultsAt 6 months, 18 of the 39 patients were asymptomatic, 10 had improved symptoms and 22 were in sinus rhythm. In the paroxysmal group, 11 were asymptomatic, 7 had improved symptoms and 16 (64%) were in sinus rhythm. In the persistent group, 7 were asymptomatic, 3 had improved symptoms and 6 (43%) were in sinus rhythm. The total group AF burden was 37.8 ± 5.4 hrs pre-procedure and 23.1 ± 5.1 hrs at 6 months post procedure. Mean temperature, impedance and power recorded at each pole demonstrated effective power delivery at all poles. No catheter charring was observed, complication rates were comparable to standard AF ablation technique.ConclusionLinear ablation in the left and right atria to mimic Cox’s Maze is feasible and safe using this ablating system.     

Semi-automated program for analysis of local Ca2+ spark release with application for classification of heart cell type

Local Ca²⁺ spark releases are essential to the Ca²⁺ cycling process. Thus, they play an important role in ventricular and atrial cell contraction, as well as in sinoatrial cell automaticity. Characterizing their properties in healthy cells from different regions in the heart can reveal the basic biophysical differences among these regions. We designed a semi-automatic Matlab Graphical User Interface (called Sparkalyzer) to characterize parameters of Ca²⁺ spark release from any major cardiac tissue, as recorded in line-scan mode with a confocal laser-scanning microscope. We validated the algorithm on experimental images from rabbit sinoatrial, atrial, and ventricular cells loaded with Fluo-4 AM. The program characterizes general image parameters of Ca²⁺ transients and sparks: spark duration, which indicates for how long the spark provides Ca²⁺ to the closed intracellular mechanisms (typical value: 25 ± 1, 23 ± 1, 26 ± 1 ms for sinoatrial, atrial, and ventricular cells, respectively); spark amplitude, which indicates the amount of Ca²⁺ released by a single spark (1.6 ± 0.1, 1.6 ± 0.2, 1.4 ± 0.1 F/F₀ for sinoatrial, atrial, and ventricular cells, respectively); spark length, which is the length of the Ca²⁺ wavelets fired out of a row of ryanodine receptors (5 ± 0.1, 5 ± 0.2, 3.4 ± 0.3 μm for sinoatrial, atrial, or ventricular cells, respectively) and number of sparks (0.14 ± 0.02, 0.025 ± 0.01, 0.02 ± 0.01 for 1 μm in 1 s for sinoatrial, atrial, and ventricular cells, respectively). This method is reliable for Ca²⁺ spark analysis of sinoatrial, atrial, or ventricular cells. Moreover, by examining the average value of Ca²⁺ spark characteristics and their scattering around the mean, atrial, ventricular and sinoatrial cells can be differentiated.     

Nonlinear synchronization assessment between atrial and ventricular activations series from the surface ECG in atrial fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia encountered in clinical practice. Its presence causes a rapid and irregular ventricular response, being the topic of intensive research in rate control therapies of AF. To this respect, recent studies suggest that ventricular response is notably influenced by atrial activity (AA) temporal organization. However, the interdependency between atrial and ventricular activations has not been adequately explored to date in real-life AF patients. The present work introduces a novel methodology to quantitatively assess synchronization and coupling between real atrial and ventricular activation series. Furthermore, the method operates on surface ECG recordings, thus providing an easy and cost-effective way to be applied. The method is based on a nonlinear index, such as cross-sample entropy (CSE), which estimates the conditional probability to find similar patterns within both activation series. The study has been carried out on patients with paroxysmal and persistent AF in order to be applied over atrial activation series with different properties in their organization. Results showed a statistically significant positive correlation between AA organization and the synchronization between atrial and ventricular activations (R = 0.53, p < 0.01). Furthermore, higher CSE values were observed for persistent (0.759 ± 0.053) than for paroxysmal AF episodes (0.662 ± 0.091), thus suggesting more synchronization between atrial and ventricular activations in paroxysmal AF. As a consequence, CSE provided findings consistent with previous works and could be used to reveal clinically useful information in the improvement of current rate control therapies, which are mainly focused on controlling ventricular rate without paying much attention to the atrial fibrillatory process.     

Determination of whole body circadian phase in lung cancer patients: melatonin vs. cortisol

Background: A quantifiable and reliable technique for the determination of body circadian phase applicable to non-laboratory studies would allow the evaluation of circadian dysregulation. In this study we evaluated feasible methodologies to individualize whole body circadian phase in lung cancer patients. Methods: Cortisol and melatonin serum levels were measured in blood samples collected every 4 h for 24 h from eleven male controls and nine men suffering from non-small cell lung cancer. Circadian rhythmicity was evaluated and the 4-hourly fractional variations (FV) were calculated to evaluate the dynamics of the rise and fall in serum levels. Results: Overall cortisol serum levels were higher in cancer patients (p < 0.001), and lower for melatonin, but not significantly (p = 0.261). Original serum levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values at night for melatonin and near awakening for cortisol. Using all data after normalization to percent of individual mean, ANOVA detected a significant time-effect (p < 0.001) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) in each group. Overall fractional variation (FV) levels were lower for cortisol in cancer patients and higher for melatonin, but these differences were not significant. FV levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values prior to darkness onset for melatonin and near mid-dark for cortisol. ANOVA also detected a significant time-effect (p < 0.002) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) for FV in each group, with maximal FV preceding maximal serum levels by ～3 h for melatonin and ～5 h for cortisol. Conclusions: A chronobiological evaluation of serum levels and fractional variations for cortisol and especially melatonin is a valuable methodology to define body circadian phase in lung cancer patients. It is possible to describe the complex process of hormone secretion with a methodology that allows the definition of both temporal characteristics and dynamic components. Impact: This kind of analysis might be useful in the study of hormone secretion(s) in cancer patients and other diseases and to guide therapeutic interventions. While lung cancer patients may have a negative prognostic value based upon stage and/or other hormonal aspects of their hypothalamus–pituitary–thyroid–adrenal axis function, patients that nevertheless maintain circadian rhythmicity in key body rhythm markers may still be eligible candidates for a chronotherapeutic approach of treatment(s).     

Asynchronisme cardiaque chez le sujet à QRS fin. Étude par échocardiographie Doppler tissulaire

ObjectiveTo assess the prevalence of different types of cardiac dyssynchrony by pulsed Doppler ultrasound and Doppler tissue in patients with narrow QRS with or without left ventricular systolic dysfunction.MethodologyProspective, cross-sectional survey at the Institute of Cardiology of Abidjan, from January to April 2012, in subjects with narrow QRS. Group 1: patients with dilated cardiomyopathy with severe left ventricular dysfunction (left ventricular end diastolic diameter greater than 60 mm and/or 30 mm/m² and ejection fraction less than 35% NYHA stage IV). Group 2: normal subjects with normal echocardiography. All patients underwent an evaluation including tissue Doppler search for different types of dyssynchrony (atrioventricular, interventricular and left intraventricular).ResultsPatients in group 1 were significantly older (51.5 ± 15.8 vs. 35.8 ± 7.8, P = 0.03), with larger left ventricular diameters and significantly higher pulmonary systolic pressure. The prevalence of different types of dyssynchrony in group 1 were: atrioventricular dyssynchrony 43.7%, interventricular dyssynchrony 37.5%, left ventricular dyssynchrony 65.6%. Group 2: atrioventricular dyssynchrony 0%, interventricular dyssynchrony 0%, left ventricular dyssynchrony 35%.ConclusionA large proportion of patients with left ventricular systolic dysfunction and narrow QRS have cardiac dyssynchrony and left ventricular dyssynchrony can be found in healthy patients. This raises the problem of the specificity of Doppler ultrasound criteria using cardiac tissue Doppler to assess cardiac dyssynchrony.     

The Use of a Quadripolar Left Ventricular Lead Increases Successful Implantation Rates in Patients with Phrenic Nerve Stimulation and/or High Pacing Thresholds Undergoing Cardiac Resynchronisation Therapy with Conventional Bipolar Leads

BackgroundPhrenic nerve stimulation (PNS) and high pacing thresholds (HPT) hinder biventricular stimulation in patients (pts) undergoing cardiac resynchronization therapy (CRT). A new quadripolar left ventricular (LV) lead (Quartet 1458Q, St. Jude Medical) with increased number of pacing configuration, might overcome this problem.MethodsAll consecutive pts in whom a standard bipolar lead intraoperatively resulted in PNS and/or HPT (≥ 4.00 V/1 mV), received, during the same implant, a quadripolar LV lead. Aim of the study was to evaluate acute and short term outcome.Results26 pts [24 (92%) male, mean age 74 ± 6 years)] with PNS (22 pts; 85%) and HPT (4 pts; 15%) were included. Permanent right ventricular pacing was the reason for broad QRS complex in 4 (15%) pts, whereas all other pts had a left bundle branch block. Severely symptomatic (NYHA Class ≥ 3) heart failure with reduced ejection fraction (EF 31 ± 9%) was mostly caused by ischemic heart disease (14 pts; 54%). Idiopathic dilated cardiomyopathy and valvular heart disease were diagnosed in 6 (23%) pts each. In most (24/26, 92%) pts the use of the Quartet lead led to successful biventricular pacing due to a significant reduction in intraoperative pacing threshold (5.2 V/1.0 ms vs. 1.4 V/0.8 ms; p = 0.03), which was maintained (1.2 V/0.7 ms) at follow-up. PNS never represented reason for failed LV pacing, neither acutely nor during follow-up.ConclusionsExcessively HPT and/or PNS are frequently encountered when conventional bipolar leads are used for CRT. A new quadripolar LV lead increases the rate of successful biventricular stimulation. Lower pacing threshold and freedom from PNS are maintained at follow-up.     

The increase in rat ventricular automaticity induced by salbutamol is mediated through β(1)- but not β(2)-adrenoceptors: role of phosphodiesterases

AimsWhile β₂-adrenoceptor (AR) agonists are useful bronchodilators, they also produce cardiac arrhythmias. These agents are not fully selective and also activate β₁-AR, but the involvement of β₁-AR and β₂-AR in the observed pro-arrhythmic effect has not been established. We studied the effect of β₁-AR and β₂-AR activation on ventricular automaticity and the role of phosphodiesterases (PDE) in regulating this effect.Main methodsExperiments were performed in the spontaneously beating isolated right ventricle of the rat heart. We also measured cAMP production in this tissue.Key findingsThe β₂-AR agonist salbutamol (1-100 μM) produced a concentration-dependent increase in ventricular automaticity that was not affected by 50 nM of the β₂-AR antagonist ICI 118551. This effect was enhanced by the non-selective PDE inhibitor theophylline (100 μM) and by the selective PDE4 inhibitors rolipram (1 μM) and Ro 201724 (2 μM), but not modified by the selective PDE3 inhibitors cilostamide (0.3 μM) or milrinone (0.2 μM). The effects of salbutamol alone and in the presence of either theophylline or rolipram were virtually abolished by 0.1 μM β₁-AR antagonist CGP20712A. Salbutamol (10 μM) increased the cAMP concentration, and this effect was abolished by CGP 20712A (0.1 μM) but enhanced by theophylline (100 μM) or rolipram (1 μM). Cilostamide (0.3 μM) failed to modify the effect of salbutamol on cAMP concentration.SignificanceThese results indicate that the increase of ventricular automaticity elicited by salbutamol was exclusively mediated through β₁-AR and enhanced by non-selective PDE inhibition with theophylline or selective PDE4 inhibition. However, PDE3 did not appear to regulate this effect.     

Efficacy of olmesartan and nifedipine on recurrent hypoxia-induced left ventricular remodeling in diabetic mice

AimsRecurrent hypoxia due to sleep apnea syndrome is implicated in cardiovascular events, especially in diabetic patients, but the underlying mechanisms remain controversial. We previously reported that angiotensin II receptor blockers can improve hypoxia-induced left ventricular remodeling. The aim of this study was to examine the effect on left ventricular remodeling of adding a calcium channel blocker to angiotensin II receptor blocker therapy in diabetic mice exposed to recurrent hypoxia.Main methodsMale db/db mice (8-week-old) and age-matched control db/+ mice were fed a Western diet and subjected to recurrent hypoxia (oxygen at 10 ± 0.5% for 8 h daily during the daytime) or normoxia for 3 weeks. Hypoxic db/db mice were treated with the vehicle, olmesartan (3 mg/kg/day), nifedipine (10 mg/kg/day), or both drugs.Key findingsRecurrent hypoxia caused hypertrophy of cardiomyocytes, interstitial fibrosis, and a significant increase in expression of the oxidative stress marker 4-hydroxy-2-nonenal (4-HNE) in the left ventricular myocardium. Treatment with olmesartan, nifedipine, or both drugs had no effect on systolic blood pressure, and each treatment achieved similar suppression of 4-HNE expression. Olmesartan and the combination with olmesartan and nifedipine significantly prevented cardiomyocyte hypertrophy more than treatment with nifedipine alone. On the other hand, olmesartan combined with nifedipine significantly reduced cytokine expression, superoxide production and matrix metalloproteinase (MMP)-9 activity, and significantly suppressed interstitial fibrosis in the left ventricular myocardium.SignificanceThe combination with olmesartan and nifedipine, as well as a monotherapy with olmesartan, exerts preferable cardioprotection in diabetic mice exposed to recurrent hypoxia.     

Three-dimensional comparison of static and dynamic scapular motion tracking techniques

The shoulder is complex and comprised of many moving parts. Accurately measuring shoulder rhythm is difficult. To classify shoulder rhythm and identify pathological movement, static measures have been the preferred method. However, dynamic measures are also used and can be less burdensome to obtain. The purpose of this paper was to determine how closely dynamic measures represent static measures using the same acromion marker cluster scapular tracking technique. Five shoulder angles were assessed for 24 participants using dynamic and static tracking techniques during humeral elevation in three planes (frontal, scapular, sagittal). ANOVAs were used to identify where significant differences existed for the factors of plane, elevation angle, and tracking technique (static, dynamic raising, dynamic lowering). All factors were significantly different for all shoulder angles (p < 0.001), except for elevation plane in scapulothoracic protraction/retraction (p = 0.955). Tracking techniques were influential (p < 0.001), but the grouped mean differences fell below a clinically relevant 5° benchmark. There was large variation in mean differences of the techniques across individuals. While population averages are similar, individual static and dynamic shoulder assessments may be different. Caution should be taken when dynamic shoulder assessments are performed on individuals, as they may not reflect those obtained in static scapular motion tracking.     

Saliva as a medium for aldosterone measurement in repeated sampling studies

BackgroundSaliva is a readily available biological fluid, making it convenient in diagnosis of diseases and in multi-sampling protocols. Several salivary steroids give a useful index of free plasma levels. Increased incidence of primary aldosteronism (PA) in approximately 10% of the hypertensive population has increased interest in the mineralocorticoid aldosterone.MethodsA biotinylated-aldosterone tracer and a commercially available antibody are used in a time-resolved fluorescence immunoassay (TR-FIA) to measure salivary aldosterone (SA). Saliva was collected in various multi-sampling protocols: Investigation of diurnal rhythm in healthy and PA patients, ACTH stimulation test and posture test in healthy subjects.ResultsMethod validation showed a sensitivity of 19 ng/L and intra-/inter-assay precision between 7.2–10.1% and 8.7–15.7%, respectively. SA correlated significantly (y = 0.2995x ± 0.01, r² = 0.60) to plasma aldosterone measured by a commercial radioimmunoassay. SA (median; 95%CI) was at 111 (95–127) ng/L in PA (n = 84) and 50 (44–56) ng/L in healthy subjects (n = 60). After change in posture, aldosterone increased in both, saliva (57 (47–63) ng/L to 95 (84–117) ng/L) and plasma (26 (26–41) ng/L to 135 (110–181) ng/L). Peak levels were reached after 1 h, and were higher in females than in males.ConclusionsSA correlates well to plasma aldosterone and mirrors responses during conditions of stress. SA is significantly higher in PA, and the diurnal rhythm seen in the healthy is blunted in PA. We additionally found gender-dependent differential responses to posture, with higher increases in females. Measurement of aldosterone in saliva presents a useful and convenient method for application in multi-sampling studies.     

Effect of preischemic β-adrenoceptor stimulation on postischemic contractile dysfunction

AimsShort periods of preischemic β-adrenoceptor stimulation protect hearts against postischemic left ventricular dysfunction. It was the aim of this study to decide whether this procedure mimics ischemic preconditioning by the generation of preischemic hemodynamic and energetic stress or whether it represents an endogenous phenomenon and to investigate the influence of age and hypertension.Main methodsIsolated rat hearts were investigated ex vivo by Langendorff perfusion and exposed to an established ischemia/reperfusion protocol (45 min no-flow ischemia and 90 min reperfusion). Left ventricular developed pressure (LVDP), rate pressure product, and ± dP/dt were analyzed.Key findingsIsoprenaline concentration dependently increased LVDP up to 40 ± 15 mm Hg (approximately EC₅₀ of 9.9 ± 0.5 nM). Isoprenaline given prior to ischemia attenuated the subsequent postischemic ventricular dysfunction (approximately EC₅₀ of 1.4 ± 0.2 pM). However, concentrations high enough to improve LVDP in normoxic hearts did not improve postischemic recovery albeit a significant reduction of hypercontraction-induced cell damage. The effect on functional recovery was attenuated by atenolol, H89, and wortmannin suggesting that β-adrenoceptor stimulation, protein kinase A, and PI 3-kinase activation are involved. The effect was conserved in hearts from 13 month old rats but lost in age-matched spontaneously hypertensive rats.SignificanceThe study identifies preischemic β-adrenoceptor stimulation as a pharmacological preconditioning protocol that does not simply mimic classical ischemic preconditioning by induction of hemodynamic or energetic stress prior to a prolonged ischemic period. The observed loss of effectiveness in hypertensives may contribute to the reduced ischemic tolerance of hypertensives.     

The cardioprotective effect of different doses of vasopressin (AVP) against ischemia–reperfusion injuries in the anesthetized rat heart

The aim of the present study was to investigate the protective effect of various doses of exogenous vasopressin (AVP) against ischemia–reperfusion injury in anesthetized rat heart. Anesthetized rats were randomly divided into seven groups (n = 4–13) and all of them subjected to prolonged 30 min regional ischemia and 120 min reperfusion. Group I served as saline control with ischemia, in treatment groups II, III, IV and V, respectively different doses of AVP (0.015, 0.03, 0.06 and 1.2 μg/rat) were infused within 10 min prior to ischemia, in group VI, an AVP-selective V1 receptor antagonist (SR49059, 1 mg/kg, i.v.) was administrated prior to effective dose of AVP injection and in group VII, SR49059 (1 mg/kg, i.v.) was only administrated prior to ischemia. Various doses of AVP significantly prevented the decrease in heart rate (HR) at the end of reperfusion compared to their baseline and decreased infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB) and MDA (malondialdehyde) plasma levels], severity and incidence of ventricular arrhythmia, episodes and duration of ventricular tachycardia (VT) as compared to control group. Blockade of V1 receptors by SR49059 attenuated the cardioprotective effect of AVP on ventricular arrhythmias and biochemical parameters, but partially returned infarct size to control. AVP 0.03 μg/rat was known as effective dose. Our results showed that AVP owns a cardioprotective effect probably via V1 receptors on cardiac myocyte against ischemia/reperfusion injury in rat heart in vivo.     

Évaluation de la fonction ventriculaire gauche par l’utilisation d’une caméra à semi-conducteur Cadmium Zinc Telluride (CZT) : impact de l’échantillonnage temporel (8 vs 16 intervalles)

BackgroundNew CZT cameras provide an increased spatial resolution and sensitivity. The tomographic acquisition “in list mode” allows the evaluation of the left ventricular function using 8–16 intervals per cycle with an increased spatial resolution. However, the impact of temporal sampling on evaluation of the contractile function remains uncertain.Method^99mTc-sestamibi SPECT studies were acquired in 99 consecutive patients (70 men, 29 women) using an ultrafast CZT Camera (D-Spectrum, Spectrum Dynamics) and processed using both 8- and 16-interval (int). All patients underwent a stress (2 MBq/kg)-rest (6 MBq/kg) single day (stop condition: 700 KCTS within a myocardial VOI). Left ventricular function was assessed using QGS^®. Perfusion was analyzed using QPS^® and quantified using Summed Stress Score (SSS), Summed Rest Score (SRS) and Summed Difference Score (SDS) (17 segments model) and the extent of perfusion defects (% of LV).ResultsEight intervals gating overestimated the end-systolic volumes (ESV) and underestimated the left ventricular ejection fraction (LVEF) compared to 16 intervals (respectively for eight and 16 intervals: at rest [VTS: 45 ± 25 mL vs 41 ± 24 mL, P < 0.0001, LVEF: 53 ± 10% vs 59 ± 10%, P < 0.0001], and post-stress [VTS: 43 ± 24. mL vs 39 ± 24 mL, P < 0.0001; LVEF: 58 ± 10% vs 61 ± 11%, P < 0.0001]). However, it was not found significant differences between end diastolic volumes (EDV) (at rest: EDV: 98 ± 33 mL vs 97 ± 33 mL, P = NS; and post-stress: EDV: 98 ± 33 ml vs 99 ± 34 mL, P = NS). Parameters of left ventricular function were consistent between eight and 16 intervals (EDV: CCC = 0.99, ESV: CCC = 0.98, LVEF: CCC = 0.92, P < 0.0001). Correlation could not be evidenced between the extent of perfusion defect and the difference between eight and 16 intervals for the different parameters of left ventricular function both at rest and post-stress.ConclusionIn our study, comparison between eight and 16 intervals showed an overestimation of the ESV and an underestimation of LVEF, without correlation with perfusion abnormalities. The estimation of LVEF on CZT camera should take into account the chosen temporal sampling.     

Intérêt potentiel des images paramétriques des temps d’éjection et de relaxation en tomoscintigraphie des cavités cardiaques dans l’évaluation des cardiopathies asynchrones

Intraleft dyssynchrony is strongly correlated to contractile dysfunction associated to severe heart failure. Dyssynchrony is also a predictive marker for cardiac resynchronization therapy response. We measured dyssynchrony values for both ventricles from gated blood pool SPECT images.Material and methodsThree groups of patients were sampled from normal patients (n = 7), mild heart failure patients (n = 24) and severe heart failure patients (n = 9). Time-derivative parametric images were obtained from 24-time bins gated blood pool SPECT data. We measured intraleft and interventricular contractile and relaxing dyssynchrony values from these images.ResultsIntraleft dispersions values linked to ventricular peak emptying rate were 107 ± 21 ms, 141 ± 58 ms and 515 ± 104 ms for each of the three groups. The values linked to left ventricular peak filling rate were 122 ± 62 ms, 219 ± 117 ms and 603 ± 164 ms respectively. Statistical significant differences (p < 0.01) were observed both for contractile and relaxing phases for severe heart failure patients. Mild heart failure patients had isolated statistical significant (p < 0.01) alterations of the ventricular relaxing phase. Correlation between isotopic dyssynchrony values and left ejection fraction led to a R square coefficient of 0.71 and 0.64 for time to peak emptying and to peak filling respectively. Correlation to QRS width values led to a R square coefficient of 0.76 and 0.62 respectively.ConclusionVentricular dyssynchrony correlated to the importance of the ventricular mechanical dysfunctions is a robust predictor of heart failure. Separate analysis of contractile and relaxing dyssynchrony may lead to a better understanding and characterization of the mechanical dysfunctions involved in heart failure.     

Plasma globotriaosylsphingosine: Diagnostic value and relation to clinical manifestations of Fabry disease

Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha-Galactosidase A, causing accumulation of globotriaosylceramide and elevated plasma globotriaosylsphingosine (lysoGb3). The diagnostic value and clinical relevance of plasma lysoGb3 concentration was investigated. All male and adult female patients with classical Fabry disease could be discerned by an elevated plasma lysoGb3. In young pre-symptomatic Fabry heterozygotes, lysoGb3 levels can be normal. Individuals carrying the R112H and P60L mutations, without classical Fabry symptoms, showed no elevated plasma lysoGb3. Multiple regression analysis showed that there is no correlation of plasma lysoGb3 concentration with total disease severity score in Fabry males. However, plasma lysoGb3 concentration did correlate with white matter lesions (odds ratio: 6.1 per 100 nM lysoGb3 increase (95% CI: 1.4–25.9, p = 0.015). In females, plasma lysoGb3 concentration correlated with overall disease severity. Furthermore, plasma lysoGb3 level was related to left ventricular mass (19.5 ± 5.5 g increase per 10 nM lysoGb3 increase; p = 0.001). In addition, it was assessed whether lifetime exposure to lysoGb3 correlates with disease manifestations. Male Fabry patients with a high lysoGb3 exposure (> 10,000 U), were moderately or severely affected, only one mildly. Female patients with a low exposure (< 1000 U) were asymptomatic or mildly affected. A large proportion of the females with an exposure > 1000 U showed disease complications. Plasma lysoGb3 is useful for the diagnosis of Fabry disease. LysoGb3 is an independent risk factor for development of cerebrovascular white matter lesions in male patients and left ventricular hypertrophy in females. Disease severity correlates with exposure to plasma lysoGb3.     

The effect of inspiratory and expiratory loads on abdominal muscle activity during breathing in subjects “at risk” for the development of chronic obstructive pulmonary disease and healthy

The abdominal muscle activity has been shown to be variable in subjects with chronic obstructive pulmonary disease (COPD) when respiratory demand increases and their recruitment pattern may change the mechanics, as well as the work and cost of breathing. The scientific evidence in subjects “at risk” for the development of COPD may be important to understand the natural history of this disease. This study aims to evaluate the effect of inspiratory and expiratory loads on the abdominal muscle activity during breathing in subjects “at risk” for the development of COPD and healthy. Thirty-one volunteers, divided in “At Risk” for COPD (n = 17; 47.71 ± 5.11 years) and Healthy (n = 14; 48.21 ± 6.87 years) groups, breathed at the same rhythm without load and with 10% of the maximal inspiratory or expiratory pressures, in standing. Surface electromyography was performed to assess the activation intensity of rectus abdominis (RA), external oblique and transversus abdominis/internal oblique (TrA/IO) muscles, during inspiration and expiration. During inspiration, in “At Risk” for COPD group, RA muscle activation was higher with loaded expiration (p = 0.016); however, in Healthy group it was observed a higher activation of external oblique and TrA/IO muscles (p < 0.050). During expiration, while in “At Risk” for COPD group, RA muscle activation was higher with loaded inspiration (p = 0.009), in Healthy group TrA/IO muscle showed a higher activation (p = 0.025). Subjects “at risk” for the development of COPD seemed to have a specific recruitment of the superficial layer of ventrolateral abdominal wall for the mechanics of breathing.     

Canine bone marrow mesenchymal stromal cells with lentiviral mHCN4 gene transfer create cardiac pacemakers

Background aimsThe study objective was to test the ability of canine mesenchymal stromal cells (cMSC) transfected with the mouse hyperpolarization-activated cyclic nucleotide-gated channel 4 (mHCN4) gene to deliver a biologic pacemaker to the canine heart.Methods and ResultscMSC that were transfected by lentiviral vector with the cardiac pacemaker gene mHCN4 expressed high levels of Cs⁺ -sensitive current (26.4 ± 1.8pA/pF at –140 mV; (n = 17) and were activated in the diastolic potential range with a reversal potential of –29.7 ± 2.5 mV (n = 14), confirming that the expressed current was Funny current (I_f)-like. Next, 3 × 10⁶ cMSC transfected with either control plasmid or the mHCN4 gene construct were injected subepicardially into the canine right ventricular wall in situ. During sinus arrest, all control hearts had spontaneous atrioventricular node rhythms [rate = 21 ± 5beats per minute (b.p.m.)]. In the mHCN4 group, six of eight animals developed spontaneous ventricular rhythms of right-sided origin (rate = 45 ± 9b.p.m.; P < 0.01). Moreover, immunohistochemical analysis of the injected regions demonstrated neither apoptosis nor cellular or humoral rejection at 2 weeks.ConclusionsThese results demonstrate that genetically modified cMSC can express functional HCN4 channels in vitro and in vivo and represent a novel delivery system for pacemaker genes into the heart.