Left ventricular endocardial pacing in cardiac resynchronisation therapy: Moving from bench to bedside

In cardiac resynchronisation therapy, failure to implant a left ventricular lead in a coronary sinus branch has been reported in up to 10% of cases. Although surgical insertion of epicardial leads is considered the standard alternative, this is not without morbidity and technical limitations. Endocardial left ventricular pacing can be an alternative as it has been associated with a favourable acute haemodynamic response compared with epicardial pacing in both animal and human studies. In this paper, we discuss left ventricular endocardial pacing and compare it with epicardial surgical implantation. Ease of application and procedural complications and morbidity compare favourably with epicardial surgical techniques. However, with limited experience, the most important concern is the still unknown long-term risk of thromboembolic complications. Therefore, for now endovascular implants should remain reserved for severely symptomatic heart failure patients and patients at high surgical risk of failed coronary sinus implantation.     

Haemodynamic evaluation of alternative left ventricular endocardial pacing sites in clinical non-responders to cardiac resynchronisation therapy

Introduction

Non response to cardiac resynchronisation therapy (CRT) may be related to the position of the coronary sinus lead.

Methods

We studied the acute haemodynamic response (AHR) from alternative left ventricular (LV) endocardial pacing sites in clinical non-responders to CRT. AHR and the interval from QRS onset to LV sensing (Q-LV interval) from four different endocardial pacing sites were evaluated in 24 clinical non-responders. A rise in LVdP/dtmax ≥ 15 % from baseline was considered a positive AHR. We also compared the AHR from endocardial with the corresponding epicardial lead position.

Results

The implanted system showed an AHR ≥ 15 % in 5 patients. In 9 of the 19 remaining patients, AHR could be elevated to ≥ 15 % by endocardial LV pacing. The optimal endocardial pacing site was posterolateral. There was no significant difference in AHR between the epicardial and the corresponding endocardial position. The longest Q-LV interval corresponded with the best AHR in 12 out of the 14 patients with a positive AHR, with an average Q-LV/QRS width ratio of 90 %.

Conclusions

Acute haemodynamic testing may indicate an alternative endocardial pacing site with a positive AHR in clinical non-responders. The Q-LV interval is a strongly correlated with the optimal endocardial pacing site. Endocardial pacing opposite epicardial sites does not result in a better AHR.     

A hybrid graph-based approach for right ventricle segmentation in cardiac MRI by long axis information transition

Right ventricle segmentation is a challenging task in cardiac image analysis due to its complex anatomy and huge shape variations. In this paper, we proposed a semi-automatic approach by incorporating the right ventricle region and shape information into livewire framework and using one slice segmentation result for the segmentation of adjacent slices. The region term is created using our previously proposed region growing algorithm combined with the SUSAN edge detector while the shape prior is obtained by forming a signed distance function (SDF) from a set of binary masks of the right ventricle and applying PCA on them. Short axis slices are divided into two groups: primary and secondary slices. A primary slice is segmented by the proposed modified livewire and the livewire seeds are transited to a pre-processed version of upper and lower slices (secondary) to find new seed positions in these slices. The shortest path algorithm is applied on each pair of seeds for segmentation. This method is applied on 48 MR patients (from MICCAI’12 Right Ventricle Segmentation Challenge) and yielded an average Dice Metric of 0.937 ± 0.58 and the Hausdorff Distance of 5.16 ± 2.88 mm for endocardium segmentation. The correlation with the ground truth contours were measured as 0.99, 0.98, and 0.93 for EDV, ESV and EF respectively. The qualitative and quantitative results declare that the proposed method outperforms the state-of-the-art methods that uses the same dataset and the cardiac global functional parameters are calculated robustly by the proposed method.     

Assessment of left ventricular ejection fraction in patients eligible for ICD therapy: Discrepancy between cardiac magnetic resonance imaging and 2D echocardiography

Objective

Implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) have substantially improved the survival of patients with cardiomyopathy. Eligibility for this therapy requires a left ventricular ejection fraction (LVEF) <35 %. This is largely based on studies using echocardiography. Cardiac magnetic resonance imaging (CMR) is increasingly utilised for LVEF assessment, but several studies have shown differences between LVEF assessed by CMR and echocardiography. The present study compared LVEF assessment by CMR and echocardiography in a heart failure population and evaluated effects on eligibility for device therapy.

Methods

152 patients (106 male, mean age 65.5 ± 9.9 years) referred for device therapy were included. During evaluation of eligibility they underwent both CMR and echocardiographic LVEF assessment. CMR volumes were computed from a stack of short-axis images. Echocardiographic volumes were computed using Simpson’s biplane method.

Results

The study population demonstrated an underestimation of end-diastolic volume (EDV) and end-systolic volume (ESV) by echocardiography of 71 ± 53 ml (mean ± SD) and 70 ± 49 ml, respectively. This resulted in an overestimation of LVEF of 6.6 ± 8.3 % by echocardiography compared with CMR (echocardiographic LVEF 31.5 ± 8.7 % and CMR LVEF 24.9 ± 9.6 %). 28 % of patients had opposing outcomes of eligibility for cardiac device therapy depending on the imaging modality used.

Conclusion

We found EDV and ESV to be underestimated by echocardiography, and LVEF assessed by CMR to be significantly smaller than by echocardiography. Applying an LVEF cut-off value of 35 %, CMR would significantly increase the number of patients eligible for device implantation. Therefore, LVEF cut-off values might need reassessment when using CMR.     

CMR-derived TAPSE measurement: a semi-quantitative method of right ventricular function assessment in patients with hypertrophic cardiomyopathy

Aim

To compare cardiovascular magnetic resonance (CMR)-derived right ventricular fractional shortening (RVFS), tricuspid annular plane systolic excursion with a reference point within the right ventricular apex (TAPSE_in) and with one outside the ventricle (TAPSE_out) with the standard volumetric approach in patients with hypertrophic cardiomyopathy (HCM).

Methods and results

105 patients with HCM and 20 healthy subjects underwent CMR. In patients with HCM, TAPSE_in (r = 0.31, p = 0.001) and RVFS (r = 0.35, p = 0.0002) revealed a significant but weak correlation with right ventricular ejection fraction (RVEF), whereas TAPSE_out (r = 0.57, p < 0.0001) showed a moderate correlation with RVEF. The ability to predict RVEF < 45 % in HCM patients was best for TAPSE_out. In patients with hypertrophic obstructive cardiomyopathy (HOCM), RVEF showed a significant but weak correlation with TAPSE_out (r = 0.36, p = 0.02) and no correlation with TAPSE_in (r = 0.05, p = 0.07) and RVFS (r = 0.02, p = 0.2). In patients with hypertrophic non-obstructive cardiomyopathy (HNCM), there was a moderate correlation between RVEF and TAPSE_out (r = 0.57, p < 0.0001) and a weak correlation with TAPSE_in (r = 0.39, p = 0.001) and RVFS (r = 0.38, p = 0.002). In the 20 healthy controls, there was a strong correlation between RVEF and all semi-quantitative measurements.

Conclusion

CMR-derived TAPSE_in is not suitable to determine right ventricular function in HCM patients. TAPSE_out showed a good correlation with RVEF in HNCM patients but only a weak correlation in HOCM patients. TAPSE_out might be used for screening but the detection of subtle changes in RV function requires the 3D volumetric approach.     

Association of apical rocking with super-response to cardiac resynchronisation therapy

Background

Super-responders to cardiac resynchronisation therapy (CRT) show an exceptional improvement in left ventricular ejection fraction (LVEF). Previous studies showed that apical rocking was independently associated with echocardiographic response to CRT. However, little is known about the association between apical rocking and super-response to CRT.

Objectives

To determine the independent association of LV apical rocking with super-response to CRT in a large cohort.

Methods

A cohort of 297 consecutive heart failure patients treated with primary indication for CRT-D were included in an observational registry. Apical rocking was defined as motion of the left ventricular (LV) apical myocardium perpendicular to the LV long axis. ‘Super-response’ was defined by the top quartile of LVEF response based on change from baseline to follow-up echocardiogram. Best-subset regression analysis identified predictors of LVEF super-response to CRT.

Results

Apical rocking was present in 45 % of patients. Super-responders had an absolute mean LVEF increase of 27 % (LVEF 22.0 % ± 5.7 at baseline and 49.0 % ± 7.5 at follow-up). Apical rocking was significantly more common in super-responders compared with non-super-responders (76 and 34 %, P < 0.001). In univariate analysis, female gender (OR 2.39, 95 % CI 1.38–4.11), lower LVEF at baseline (OR 0.91 95 % CI 0.87–0.95), non-ischaemic aetiology (OR 4.15, 95 % CI 2.33–7.39) and apical rocking (OR 6.19, 95 % CI 3.40–11.25) were associated with super-response. In multivariate analysis, apical rocking was still strongly associated with super-response (OR 5.82, 95 % CI 2.68–12.61). Super-responders showed an excellent clinical prognosis with a very low incidence of heart failure admission, cardiac mortality and appropriate ICD therapy.

Conclusion

Apical rocking is independently associated with super-response to CRT.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0768-4) contains supplementary material, which is available to authorized users.     

NF-RCNN: Heart localization and right ventricle wall motion abnormality detection in cardiac MRI

Convolutional neural networks (CNNs) are extensively used in cardiac image analysis. However, heart localization has become a prerequisite to these networks since it decreases the size of input images. Accordingly, recent CNNs benefit from deeper architectures in gaining abstract semantic information. In the present study, a deep learning-based method was developed for heart localization in cardiac MR images. Further, Network in Network (NIN) was used as the region proposal network (RPN) of the faster R-CNN, and then NIN Faster-RCNN (NF-RCNN) was proposed. NIN architecture is formed based on “MLPCONV” layer, a combination of convolutional network and multilayer perceptron (MLP). Therefore, it could deal with the complicated structures of MR images. Furthermore, two sets of cardiac MRI dataset were used to evaluate the network, and all the evaluation metrics indicated an absolute superiority of the proposed network over all related networks. In addition, FROC curve, precision-recall (PR) analysis, and mean localization error were employed to evaluate the proposed network. In brief, the results included an AUC value of 0.98 for FROC curve, a mean average precision of 0.96 for precision-recall curve, and a mean localization error of 6.17 mm. Moreover, a deep learning-based approach for the right ventricle wall motion analysis (WMA) was performed on the first dataset and the effect of the heart localization on this algorithm was studied. The results revealed that NF-RCNN increased the speed and decreased the required memory significantly.     

Anodal stimulation: an underrecognized cause of nonresponders to cardiac resynchronization therapy

Objective

The purpose of this study was to determine if anodal stimulation accounts for failure to benefit from cardiac resynchronization therapy (CRT) in some patients.

Background

Approximately 30-40% of patients with moderate to severe heart failure do not have symptomatic nor echocardiographic improvement in cardiac function following CRT. Modern CRT devices allow the option of programming left ventricular (LV) lead pacing as LV tip to right ventricular (RV) lead coil to potentially improve pacing thresholds. However, anodal stimulation can result in unintentional RV pacing (anode) instead of LV pacing (cathode).

Methods

Patients enrolled in our center''s CRT registry had an echocardiogram, 6-minute walk (6MW), and Minnesota Living with HF Questionnaire (MLHFQ) pre-implant and 6 months after CRT. Electrocardiograms (12 lead) during RV, LV, and biventricular (BiV) pacing were obtained at the end of the implant in 102 patients. Anodal stimulation was defined as LV pacing QRS morphology on EKG being identical to RV pacing or consistent with fusion with RV and LV electrode capture. LV end systolic volume (LVESV) was measured by echo biplane Simpson''s method and CRT responder was defined as 15% or greater reduction in LVESV.

Results

Of the 102 patients, 46 (45.1%) had the final LV lead pacing configuration programmed LV (tip or ring) to RV (coil or ring). 3 of the 46 subjects (6.5%) had EKG findings consistent with anodal stimulation, not corrected intraoperatively. All anodal stimulation patients were nonresponders to CRT by echo criteria (reduction in LVESV 13.3 ± 0.6%, increase in EF 5.0 ± 1.4%) compared to 46% responders for those without anodal stimulation, (change in LVESV 18.7 ± 25.6%, EF 7.6 ±10.9%). None of the anodal stimulation patients were responders for the 6 minute walk, compared to 32 of 66 (48%) of those without anodal stimulation.

Conclusion

Anodal stimulation is a potential underrecognized and ameliorable cause of poor response to CRT.     

Tailoring cardiac resynchronisation therapy to non-left bundle branch block: Successful cardiac resynchronisation for right bundle branch block with left posterior fascicular block without implantation of a left ventricular lead

Despite advances, cardiac resynchronisation therapy (CRT) remains fundamentally orientated to the dyssynchrony of left bundle branch block (LBBB), in which septo-lateral electrical and mechanical delays predominate. For non-LBBB patients response rates to conventional CRT are lower and mortality and rehospitalisation rates are not reduced. Despite this, alternative approaches which tailor CRT to the differing dyssynchrony patterns of non-LBBB have yet to be developed. In the specific non-LBBB subgroup of right bundle branch block (RBBB) with left posterior fascicular block (LPFB), ventricular conduction via the left anterior fascicle results in a unique early lateral, and late septal depolarisation, or lateral to septal left ventricular (LV) delay, an electrical sequence which is followed mechanically. This latero-septal delay is somewhat the reverse of LBBB and was overcome by fusing right ventricular (RV) septal pacing with intrinsic conduction via the left anterior fascicle, achieving successful resynchronisation without implantation of a left ventricular lead. A stable fusion pattern was achieved via the ‘Negative AV Hysteresis with Search’ algorithm (Abbott, St Paul, Minnesota). Improvement in all standard CRT response indices was achieved at 3 months: QRS duration was reduced from 153 to 106 ms, ejection fraction increased from 14 to 32%, and LV end-systolic and end-diastolic diameters reduced by 19% and 12.5% respectively. NYHA class improved from III-IV to class II. Cardiac resynchronisation for RBBB with LPFB can be successfully achieved with a standard pacemaker or defibrillator without left ventricular lead implantation by fusing RV septal-only pacing with intrinsic conduction.     

高原低氧适应动物新疆灰旱獭右心室重构的组织学改变

目的探讨新疆灰旱獭高原低氧适应性改变致右心室重构组织学改变。方法应用免疫组化技术检测新疆灰旱獭右心室缝隙连接蛋白43(CX43)蛋白表达,同时应用HE染色和Masson染色观察心室肌结构和纤维化程度变化。结果心肌细胞肥大,胶原纤维增多,右心室肥厚指数、体重指数明显增高。CX43蛋白表达减少和(或)分布的改变。结论高原低氧致新疆灰旱獭右心室结构重构,可作为研究高原低氧适应性机制的理想动物模型。     

Comparison of cortical activation patterns by somatosensory stimulation on the palm and dorsum of the hand

Abstract

Objectives: Little is known about differences of cortical activation according to body location. We attempted to compare brain activation patterns by somatosensory stimulation on the palm and dorsum of the hand, using functional magnetic resonance imaging (fMRI).

Method: We recruited 15 healthy right-handed volunteers for this study. fMRI was performed during touch stimulation using a rubber brush on an area of the same size on the palm or dorsum of the hand. Regions of interest (ROIs) were drawn at the primary sensory–motor cortex (SM1), posterior parietal cortex, and secondary somatosensory cortex.

Results: Group analysis of fMRI data indicated that touch stimulation on the palm resulted in production of more activated voxels in the contralateral SM1 and posterior parietal cortex than on the dorsum of the hand. The most activated ROI was found to be the contralateral SM1 by stimulation of the palm or dorsum, and the number of activated voxels (5875) of SM1 by palm stimulation was more than 2 times that (2282) of dorsum stimulation. The peak activated value in the SM1 by palm stimulation (16.43) was also higher than that of the dorsum (5.52).

Conclusion: We found that stimulation of the palm resulted in more cortical activation in the contralateral SM1 than stimulation of the dorsum. Our results suggested that the palm of the hand might have larger somatotopy of somatosensory representation for touch in the cerebral cortex than the dorsum of the hand. Our results would be useful as a rehabilitation strategy when more or less somatosensory stimulation of the hand is necessary.     

Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD

Background

Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD.

Methods

42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized to sedentariness or HIIT for 4 weeks. Cardiac function was evaluated by echocardiography and muscularization of pulmonary vessel walls by immunohistochemistry.

Results

Smoke exposure induced RV systolic dysfunction demonstrated by reduced tricuspid annular plane systolic excursion. HIIT in smoke-exposed mice reversed RV dysfunction. There were no significant effects on the left ventricle of neither smoke exposure nor HIIT. Muscularization of the pulmonary vessels was reduced after exercise intervention, but no significant effects on muscularization were observed from smoke exposure.

Conclusions

RV function was reduced in mice exposed to cigarette smoke. No Increase in pulmonary vessel muscularization was observed in these mice, implying that other mechanisms caused the RV dysfunction. HIIT attenuated the RV dysfunction in the smoke exposed mice. Reduced muscularization of the pulmonary vessels due to HIIT suggests that exercise training not only affects the heart muscle, but also has important effects on the pulmonary vasculature.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0117-y) contains supplementary material, which is available to authorized users.     

Marshall to the rescue in cardiac resynchronization therapy: Left ventricular lead placement in coronary sinus ostial atresia

This case highlights the importance of proper identification of congenital anomalies of the coronary sinus for the successful placement of left ventricular lead during cardiac resynchronization therapy device implantation. We discuss an alternate route for left ventricular lead placement via the vein of Marshall when the coronary sinus ostium in the right atrium was atretic and was facing difficulty initially in detecting the anomaly.     

经颅电刺激对睡眠剥夺后双侧后扣带回皮质功能连接紊乱干预作用的初步研究

目的:探讨经颅电刺激对睡眠剥夺后双侧后扣带回皮质功能连接紊乱的干预作用。方法:研究采用自身前后对照的试验设计。16名受试者均接受2次24 h睡眠剥夺,2次睡眠剥夺间隔3周,受试者分别于第1次正常睡眠后、24 h睡眠剥夺后、经颅电刺激(真或假刺激)干预后(真、假刺激电流大小均为1 mA,电流作用时间分别为20 min、2 s,干预实验均持续20 min)及第2次经颅电刺激(假或真刺激)干预后采集静息态磁共振成像数据。以睡眠剥夺前收集静息态功能磁共振数据作为基线,选取双侧后扣带回皮质作为种子点进行全脑功能连接分析,观察睡眠剥夺前后及经颅电刺激真、假刺激后大脑的功能连接变化。结果:与正常睡眠后相比,24 h睡眠剥夺后双侧后扣带回皮质与双侧丘脑间的功能连接上升(P<0.01),与右侧楔前叶、海马旁回以及双侧岛叶间的功能下降(P<0.01)。与假刺激相比,给予真刺激后左侧后扣带回皮质与右侧楔前叶功能连接上升(P<0.01);与双侧丘脑、岛叶及右侧大脑皮质功能连接下降(P<0.01)。右侧后扣带回皮质与全脑的功能连接在双侧丘脑、右侧岛叶及大脑皮层间也存在下降(P<0....     

功能磁共振和脑电神经成像技术与大脑刺激相结合的研究进展

随着对神经机制问题阐述水平的迅速提高,所应用的神经成像技术、方法及各种工具的复杂程度也在不断提高．一方面是神经成像技术本身的不断发展,另一方面则是大脑直接刺激与神经成像技术同步记录方法的发展．经颅磁刺激-功能磁共振成像同步技术(TMS-fMRI)和经颅磁刺激-脑电技术(TMS-EEG)能为研究大脑网络的功能和有效连通性提供技术手段,该技术在多种认知领域的发展和应用,为神经科学、认知心理学、神经信息学等学科的研究者对人脑的研究开启了多条通道,更加有利于深入地理解人类大脑的工作机制．     

Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction

Following the acute phase of a myocardial infarction, a set of structural and functional changes evolves in the myocardium, collectively referred to as cardiac remodeling. This complex set of processes, including interstitial fibrosis, inflammation, myocyte hypertrophy and apoptosis may progress to heart failure. Analogs of the incretin hormone glucagon-like peptide 1 (GLP-1) have shown some promise as cardioprotective agents. We hypothesized that a long-acting GLP-1 analog liraglutide would ameliorate cardiac remodeling over the course of 4 weeks in a rat model of non-reperfused myocardial infarction. In 134 male Sprague Dawley rats myocardial infarctions were induced by ligation of the left anterior descending coronary artery. Rats were randomized to either subcutaneous injection of placebo or 0.3 mg liraglutide once daily. Cardiac magnetic resonance imaging was performed after 4 weeks. Histology of the infarcted and remote non-infarcted myocardium, selected molecular remodeling markers and mitochondrial respiration in fibers of remote non-infarcted myocardium were analyzed. Left ventricular end diastolic volume increased in the infarcted hearts by 62% (from 0.58 ± 0.03 mL to 0.95 ± 0.07 mL, P < 0.05) compared to sham operated hearts and left ventricle ejection fraction decreased by 37% (63 ± 1%–40 ± 3%, P < 0.05). Increased interstitial fibrosis and phosphorylation of p38 Mitogen Activated Protein Kinase were observed in the non-infarct regions. Mitochondrial fatty acid oxidation was impaired. Liraglutide did not affect any of these alterations. Four-week treatment with liraglutide did not affect cardiac remodeling following a non-reperfused myocardial infarction, as assessed by cardiac magnetic resonance imaging, histological and molecular analysis and measurements of mitochondrial respiration.     

Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

The clinical applications of cardiovascular magnetic resonance imaging with contrast enhancement are expanding. Besides the direct visualisation of viable and non-viable myocardium, this technique is increasingly used in a variety of cardiac disorders to determine the exact aetiology, guide proper treatment, and predict outcome and prognosis. In this review, we discuss the value of cardiovascular magnetic resonance imaging with contrast enhancement in a range of cardiac disorders, in which this technique may provide insights beyond the scope of myocardial viability.     

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative <Emphasis Type="Italic">FBN1</Emphasis> mutations

Background

Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation.

Methods

In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up.

Results

Changes in biventricular dimensions were assessed in 163 Marfan patients (48?% female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. ?8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. ?18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. ?8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. ?7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28).

Conclusion

Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.