Simulated Obstructive Sleep Apnea Increases P-Wave Duration and P-Wave Dispersion

BackgroundA high P-wave duration and dispersion (Pd) have been reported to be a prognostic factor for the occurrence of paroxysmal atrial fibrillation (PAF), a condition linked to obstructive sleep apnea (OSA). We tested the hypothesis of whether a short-term increase of P-wave duration and Pd can be induced by respiratory manoeuvres simulating OSA in healthy subjects and in patients with PAF.Methods12-lead-electrocardiography (ECG) was recorded continuously in 24 healthy subjects and 33 patients with PAF, while simulating obstructive apnea (Mueller manoeuvre, MM), obstructive hypopnea (inspiration through a threshold load, ITH), central apnea (AP), and during normal breathing (BL) in randomized order. The P-wave duration and Pd was calculated by using dedicated software for ECG-analysis.ResultsP-wave duration and Pd significantly increased during MM and ITH compared to BL in all subjects (+13.1ms and +13.8ms during MM; +11.7ms and +12.9ms during ITH; p<0.001 for all comparisons). In MM, the increase was larger in healthy subjects when compared to patients with PAF (p<0.05).ConclusionIntrathoracic pressure swings through simulated obstructive sleep apnea increase P-wave duration and Pd in healthy subjects and in patients with PAF. Our findings imply that intrathoracic pressure swings prolong the intra-atrial and inter-atrial conduction time and therefore may represent an independent trigger factor for the development for PAF.     

高血压房颤与孤立性房颤的临床对比分析

目的：分析高血压房颤（HAF）与孤立性房颤（LAF）的临床特征及其对预后的影响。方法：高血压房颤患者106例,孤立性房颤患者102例,分别对其性别,年龄,家族史,并发症,持续性房颤发生情况,超声心动图等临床特征进行分析。结果：二者相比,LAF组发病年龄轻,左房增大者少,持续性房颤者少;两组中左房增大均与持续性房颤者,并发症呈正相关。高血压程度与持续性房颤者,并发症呈正相关。结论左房增大是房颤发生的主要机制,左房是否增大是判断愈后的一个重要指标。     

Orthogonal P-wave morphology is affected by intra-atrial pressures

Background

It has previously been shown that the morphology of the P-wave neither depends on atrial size in healthy subjects with physiologically enlarged atria nor on the physiological anatomical variation in transverse orientation of the left atrium. The present study aimed to investigate if different pressures in the left and right atrium are associated with different P-wave morphologies.

Methods

38 patients with isolated, increased left atrial pressure, 51 patients with isolated, increased right atrial pressure and 76 patients with biatrially increased pressure were studied. All had undergone right heart catheterization and had 12-lead electrocardiographic recordings, which were transformed into vectorcardiograms for detailed P-wave morphology analysis.

Results

Normal P-wave morphology (type 1) was more common in patients with isolated increased pressure in the right atrium while abnormal P-wave morphology (type 2) was more common in the groups with increased left atrial pressure (P = 0.032). Moreover, patients with increased left atrial pressure, either isolated or in conjunction with increased right atrial pressure, had significantly more often a P-wave morphology with a positive deflection in the sagittal plane (P = 0.004).

Conclusion

Isolated elevated right atrial pressure was associated with normal P-wave morphology while left-sided atrial pressure elevation, either isolated or in combination with right atrial pressure elevation, was associated with abnormal P-wave morphology.

     

A patient-specific approach for quantitative and automatic analysis of computed tomography images in lung disease: Application to COVID-19 patients

PurposeQuantitative metrics in lung computed tomography (CT) images have been widely used, often without a clear connection with physiology. This work proposes a patient-independent model for the estimation of well-aerated volume of lungs in CT images (WAVE).MethodsA Gaussian fit, with mean (Mu.f) and width (Sigma.f) values, was applied to the lower CT histogram data points of the lung to provide the estimation of the well-aerated lung volume (WAVE.f). Independence from CT reconstruction parameters and respiratory cycle was analysed using healthy lung CT images and 4DCT acquisitions. The Gaussian metrics and first order radiomic features calculated for a third cohort of COVID-19 patients were compared with those relative to healthy lungs. Each lung was further segmented in 24 subregions and a new biomarker derived from Gaussian fit parameter Mu.f was proposed to represent the local density changes.ResultsWAVE.f resulted independent from the respiratory motion in 80% of the cases. Differences of 1%, 2% and up to 14% resulted comparing a moderate iterative strength and FBP algorithm, 1 and 3 mm of slice thickness and different reconstruction kernel. Healthy subjects were significantly different from COVID-19 patients for all the metrics calculated. Graphical representation of the local biomarker provides spatial and quantitative information in a single 2D picture.ConclusionsUnlike other metrics based on fixed histogram thresholds, this model is able to consider the inter- and intra-subject variability. In addition, it defines a local biomarker to quantify the severity of the disease, independently of the observer.     

Paroxysmal atrial fibrillation recognition based on multi-scale wavelet <Emphasis Type="Italic">α</Emphasis>-entropy

Background

This study proposed an effective method based on the wavelet multi-scale α-entropy features of heart rate variability (HRV) for the recognition of paroxysmal atrial fibrillation (PAF). This new algorithm combines wavelet decomposition and non-linear analysis methods. The PAF signal, the signal distant from PAF, and the normal sinus signals can be identified and distinguished by extracting the characteristic parameters from HRV signals and analyzing their quantification indexes. The original ECG signals for QRS detection and HRV signal extraction are first processed. The features from the HRV signals are extracted as feature vectors using the wavelet multi-scale entropy. A support vector machine-based classifier is used for PAF prediction.

Results

The performance of the proposed method in predicting PAF episodes is evaluated with 100 signals from the MIT-BIT PAF prediction database. With regard to the dynamics and uncertainty of PAF signals, our proposed method obtains the values of 92.18, 94.88, and 89.48% for the evaluation criteria of correct rate, sensitivity, and specificity, respectively.

Conclusions

Our proposed method presents better results than the existing studies based on time domain, frequency domain, and non-linear methods. Thus, our method shows considerable potential for clinical monitoring and treatment.

     

Utilization of Electrocardiographic P-wave Duration for AV Interval Optimization in Dual-Chamber Pacemakers

Background

Empiric programming of the atrio-ventricular (AV) delay is commonly performed during pacemaker implantation. Transmitral flow assessment by Doppler echocardiography can be used to find the optimal AV delay by Ritter''s method, but this cannot easily be performed during pacemaker implantation. We sought to determine a non-invasive surrogate for this assessment. Since electrocardiographic P-wave duration estimates atrial activation time, we hypothesized this measurement may provide a more appropriate basis for programming AV intervals.

Methods

A total of 19 patients were examined at the time of dual chamber pacemaker implantation, 13 (68%) being male with a mean age of 77. Each patient had the optimal AV interval determined by Ritter''s method. The P-wave duration was measured independently on electrocardiograms using MUSE® Cardiology Information System (version 7.1.1). The relationship between P-wave duration and the optimal AV interval was analyzed.

Results

The P-wave duration and optimal AV delay were related by a correlation coefficient of 0.815 and a correction factor of 1.26. The mean BMI was 27. The presence of hypertension, atrial fibrillation, and valvular heart disease was 13 (68%), 3 (16%), and 2 (11%) respectively. Mean echocardiographic parameters included an ejection fraction of 58%, left atrial index of 32 ml/m², and diastolic dysfunction grade 1 (out of 4).

Conclusions

In patients with dual chamber pacemakers in AV sequentially paced mode and normal EF, electrocardiographic P-wave duration correlates to the optimal AV delay by Ritter''s method by a factor of 1.26.     

Correlation between the sudden jump-like increases of the atrio-Hisian interval induced during burst atrial pacing and during programmed atrial stimulation in patients with atrioventricular nodal reentrant tachycardia

Purpose

To study the correlation between the sudden prolongations of the atrio-Hisian (AH) interval with ≥50 ms during burst and programmed atrial stimulation, and to define whether the AH jump during burst atrial pacing is a reliable diagnostic criterion for dual AV nodal physiology.

Shensongyangxin Capsules for Paroxysmal Atrial Fibrillation: A Systematic Review of Randomized Clinical Trials

Objective

To evaluate the evidence for the effectiveness and safety of Shensongyangxin Capsules (SSYX) for treating paroxysmal atrial fibrillation (PAF).

Methods

We searched for randomized clinical trials for SSYX in PAF up to June 2015. The Cochrane risk of bias tool was used to assess the methodological quality. RevMan 5.3 was used to synthesize the results.

Results

We included 22 trials involving 2,347 PAF patients. The quality of the included studies was generally poor. The results of the meta-analysis showed that SSYX plus routine treatment was more effective at improving P-wave dispersion (Pwd) and the frequency of PAF attacks compared with routine treatment alone. The results from the included trials that compared SSYX plus routine treatment and arrhythmic drugs plus routine treatment were inconsistent. Trials reported on Pwd, quality of life, frequency of PAF attacks or maintenance rate of sinus rhythm and found that SSYX combined with anti-arrhythmic drugs plus routine treatment was more effective than anti-arrhythmic drugs plus routine treatment. Four of the trials reported adverse events, indicating that SSYX was potentially safer than anti-arrhythmic drugs.

Conclusions

There appears to be some benefit from the use of SSYX. However, due to poor methodological quality, we could not draw confirmative conclusions regarding the beneficial effect of using SSYX.     

The immune system as a chronotoxicity target of the anticancer mTOR inhibitor everolimus

The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing. C57BL/6J mice were synchronized with light-dark 12h:12h, with L onset at Zeitgeber Time (ZT) 0. Everolimus was administered orally to male (5 mg/kg/day) and female mice (15 mg/kg/day) at ZT1, during early rest span or at ZT13, during early activity span for 4 weeks. Body weight loss, as well as hematological, immunological and biochemical toxicities, were determined. Spleen and thymus were examined histologically. Everolimus toxicity was less severe following dosing at ZT13, as compared to ZT1, as shown with least body weight inhibition in both genders; least reductions in thymus weight both in males (p < 0.01) and females (p < 0.001), least reduction in female spleen weight (p < 0.05), and less severe thymic medullar atrophy both in males (p < 0.001) and females (p < 0.001). The mean circulating counts in total leukocytes, total lymphocytes, T-helper and B lymphocytes displayed minor and non-significant changes following dosing at ZT13, while they were decreased by 56.9% (p < 0.01), 45.5% (p < 0.01), 43.1% (p < 0.05) and 48.7% (p < 0.01) after everolimus at ZT1, respectively, in only male mice. Chronotherapy of everolimus is an effective way to increase the general tolerability and decrease toxicity on the immune system.     

Analysis of changes in the beat-to-beat P-wave morphology using clustering techniques

Several pathologies related to the atrial electrical activity can be detected in the electrocardiogram P-wave. A protocol for analyzing P-wave morphology changes has been developed in this article. By using this protocol a study on the beat-to-beat P-wave morphology changes of 89 ECG signals is performed. An algorithm based on the embedding space techniques has been used to extract the P-wave information of the ECG. The P-waves obtained in several of these ECGs exhibit significant alternate morphology changes. The morphologies have been classified by using the K-means clustering algorithm. The mechanism behind the P-wave morphology change process and its possible pathophysiological importance remains to be clarified.     

Can a partial volume edge effect reduction algorithm improve the repeatability of subject-specific finite element models of femurs obtained from CT data?

The reliability of patient-specific finite element (FE) modelling is dependent on the ability to provide repeatable analyses. Differences of inter-operator generated grids can produce variability in strain and stress readings at a desired location, which are magnified at the surface of the model as a result of the partial volume edge effects (PVEEs). In this study, a new approach is introduced based on an in-house developed algorithm which adjusts the location of the model's surface nodes to a consistent predefined threshold Hounsfield unit value. Three cadaveric human femora specimens were CT scanned, and surface models were created after a semi-automatic segmentation by three different experienced operators. A FE analysis was conducted for each model, with and without applying the surface-adjustment algorithm (a total of 18 models), implementing identical boundary conditions. Maximum principal strain and stress and spatial coordinates were probed at six equivalent surface nodes from the six generated models for each of the three specimens at locations commonly utilised for experimental strain guage measurement validation. A Wilcoxon signed-ranks test was conducted to determine inter-operator variability and the impact of the PVEE-adjustment algorithm. The average inter-operator difference in stress values was significantly reduced after applying the adjustment algorithm (before: 3.32 ± 4.35 MPa, after: 1.47 ± 1.77 MPa, p = 0.025). Strain values were found to be less sensitive to inter-operative variability (p = 0.286). In summary, the new approach as presented in this study may provide a means to improve the repeatability of subject-specific FE models of bone obtained from CT data.     

Safety and feasibility of atrial fibrillation ablation using Amigo® system versus manual approach: A pilot study

Background

The Amigo^® Remote Catheter System is a relatively new robotic system for catheter navigation. This study compared feasibility and safety using Amigo (RCM) versus manual catheter manipulation (MCM) to treat paroxysmal atrial fibrillation (PAF). Contact force (CF) and force-time integral (FTI) values obtained during pulmonary vein isolation (PVI) ablation were compared.

Association of 24 h–systolic blood pressure variability and cardiovascular disease in patients with obstructive sleep apnea

Background

To evaluate association of 24 h–systolic blood pressure (SBP) variability and obstructive sleep apnea (OSA) as defined by the apnea-hypopnea index ≥5/h; and association of 24 h–SBP variability and prevalent cardiovascular disease (CVD) in OSA patients.

Methods

Participants underwent polysomongraphy to evaluate the presence of OSA, and 24 h–ambulatory blood pressure monitoring was applied to evaluate 24 h–SBP variability as indexed by weighted 24 h–standard deviation (SD) of SBP. Between-group differences were evaluated in participants with and without OSA. Participants with OSA were divided into high and low 24 h–SBP variability groups and between-group differences were evaluated.

Results

Mean age of 384 participants was 50 years old and 42.2% had OSA. Mean 24 h–systolic/diastolic BP were 130/78 mmHg, with mean weighted 24 h–SD of systolic/diastolic BP were 12.9/7.3 mmHg. Compared to those without OSA, OSA participants had higher clinic-, 24 h-, daytime- and nighttime-SBP, and weighted 24 h, daytime- and nighttime-SD of SBP. Age, prevalent CVD and OSA, usage of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker and diuretic were significantly associated with 24 h–SBP variability. In OSA patients, compared to those with low variability, participants with high variability had higher weighted 24 h, daytime- and nighttime-SD of SBP. After adjusted for covariates including clinic-SBP and 24 h–SBP, per 1-SD increment weighted 24 h–SD of SBP was associated with 21% increased prevalent CVD.

Conclusions

Patients with newly-diagnosed OSA have higher 24 h–SBP variability compared to those without OSA; in OSA patients, increased 24 h–SBP variability is associated with increased prevalence of CVD.

     

Serum level of transforming growth factor beta 1 is associated with left atrial voltage in patients with chronic atrial fibrillation

Background

Atrial tissue fibrosis can cause electrical or structural remodeling in patients with atrial fibrillation. Transforming growth factor beta 1(TGF-β1) signaling acts as a central role in fibroblast activation. In this report, we aimed to investigate the relationship between serum level of TGF-β1 and mean left atrial voltage in patients with chronic atrial fibrillation (CAF).

Application of gas chromatography mass spectrometry (GC–MS) in conjunction with multivariate classification for the diagnosis of gastrointestinal diseases

Gastrointestinal diseases such as irritable bowel syndrome, Crohn’s disease (CD) and ulcerative colitis are a growing concern in the developed world. Current techniques for diagnosis are often costly, time consuming, inefficient, of great discomfort to the patient, and offer poor sensitivities and specificities. This paper describes the development and evaluation of a new methodology for the non-invasive diagnosis of such diseases using a combination of gas chromatography mass spectrometry (GC–MS) and chemometrics. Several potential sample matrices were tested: blood, breath, faeces and urine. Faecal samples provided the only statistically significant results, providing discrimination between CD and healthy controls with an overall classification accuracy of 85 % (78 % specificity; 93 % sensitivity). Differentiating CD from other diseases proved more challenging, with overall classification accuracy dropping to 79 % (83 % specificity; 68 % sensitivity). This diagnostic performance compares well with the gold standard technique of colonoscopy, suggesting that GC–MS may have potential as a non-invasive screening tool.     

Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background

A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms.

Methods

We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics.

Results

The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%).

Conclusion

Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations.     

Influence of segmentation on morphological parameters and computed hemodynamics in cerebral aneurysms

This article focuses on the effects of segmentation on cerebral aneurysm's morphological parameters and on blood flow patterns computed using computational fluid dynamics. Segmentation is a non-negligible source of uncertainty that may have a consequent impact on the morphological assessment and the resulting hemodynamical simulations, the latter potentially being a key element in the decision-making therapeutic armamentarium for neuroradiologists and neurosurgeons. From the three patient-specific cases investigated, medical imaging data sets were collected, and four different three-dimensional segmentations were generated by the same senior technician. Morphological parameters were measured, and the aspect ratio was derived. Numerical simulations were performed; flow pattern changes, their impact on wall shear stress (WSS) and their sensitivity within the four reconstructed geometries were analyzed. Aneurysm velocity, vorticity and shear magnitudes were computed and compared. The morphological parameters having the highest variability were the aneurysm lobe dimensions (20 %). The neck length was the second parameter presenting the highest variability (21 %). The neck width variability reached 13.8 %, and the aspect ratio variability reached 14.2 %. The artery height and the artery width presented a variability of 13.7 and 10.8 %, respectively. Finally, the aneurysm depth, aneurysm height and aneurysm width presented variabilities of 12.8, 9.4 and 7.3 %, respectively. Differences in the flow path lines, velocity magnitude, wall shear stress and vorticity are also reported and discussed. The average variability reached 15.6 % for velocity, 25.2 % for vorticity and 25.2 % for shear, these parameters being computed inside the aneurysm. The maximum variability reached 31.0 % for velocity, 54.8 % for vorticity and 58.1 % for shear. A segmentation process reconstructing anatomies that is less sensitive to human intervention would be a future goal worth pursuing.     

Feasibility of multiplane microtransoesophageal echocardiographic guidance in structural heart disease transcatheter interventions in adults

Introduction

Structural heart interventions are guided by transoesophageal or intracardiac echocardiography (TEE/ICE). MicroTEE, developed for paediatric purposes, is smaller and therefore less invasive and traumatic, avoiding the need for general anaesthesia. We aimed to show feasibility of procedural guidance by comparing image quality of microTEE with standard TEE and ICE during adult transcatheter interventions, and assess the accuracy in obtaining left atrial appendage (LAA) measurements between the microTEE probe and standard TEE.

Methods and results

We prospectively included 49 patients (20 women, 64 ± 18 years). Intraprocedural images were obtained by using the microTEE probe and standard (2D and 3D) TEE (LAA closure, MitraClip implantation) or ICE (interatrial communication closure, transseptal puncture for left atrial ablation). Two echocardiographers independently assessed image quality from 1 (excellent) to 4 (poor) and performed LAA measurements. Use of microTEE was not related to significant discomfort. Image quality obtained with the microTEE probe was lower than with standard TEE (2 [1–2] vs. 1 [1–2]; p = 0.04) and comparable with ICE images (2 [1–2] vs. 2 [1–2], p = 0.13). MicroTEE showed a wider field of view than ICE. LAA measurements on images obtained by microTEE were strongly associated with standard TEE.

Conclusions

MicroTEE seems feasible for guidance during transcatheter heart interventions in adults. MicroTEE imaging offers a wider field of view than ICE, and its accuracy is comparable with TEE. In transcatheter interventions performed under conscious sedation, microTEE might be a viable and advantageous alternative to standard TEE or ICE.

     

A Model for Mechano-Electrical Feedback Effects on Atrial Flutter Interval Variability

Atrial flutter is a supraventricular arrhythmia, based on a reentrant mechanism mainly confined to the right atrium. Although atrial flutter is considered a regular rhythm, the atrial flutter interval (i.e., the time interval between consecutive atrial activation times) presents a spontaneous beat-to-beat variability, which has been suggested to be related to ventricular contraction and respiration by mechano-electrical feedback. This paper introduces a model to predict atrial activity during atrial flutter, based on the assumption that atrial flutter variability is related to the phase of the reentrant activity in the ventricular and respiratory cycles. Thus, atrial intervals are given as a superimposition of phase-dependent ventricular and respiratory modulations. The model includes a simplified atrioventricular (AV) branch with constant refractoriness and conduction times, which allows the prediction of ventricular activations in a closed-loop with atrial activations. Model predictions are quantitatively compared with real activation series recorded in 12 patients with atrial flutter. The model predicts the time course of both atrial and ventricular time series with a high beat-to-beat agreement, reproducing 96±8% and 86±21% of atrial and ventricular variability, respectively. The model also predicts the existence of phase-locking of atrial flutter intervals during periodic ventricular pacing and such results are observed in patients. These results constitute evidence in favor of mechano-electrical feedback as a major source of cycle length variability during atrial flutter.