Evaluation of Left Ventricular Endocardial Cardiac Resynchronization Therapy in a Non-responder with Ventricular Arrhythmias

Approximately one third of patients treated with cardiac resynchronization therapy do not derive any detectable benefit. In these patients, acute invasive hemodynamic evaluation can be used for therapy optimization. This report describes the use of systematic invasive hemodynamic measurements for clinical decision making in a patient who experienced severe ventricular arrhythmias and clinical deterioration following a biventricular upgrade.     

短暂中断慢性心力衰竭患者心脏再同步化治疗后心脏运动同步性变化的临床研究

目的：观察短暂中断心脏再同步化治疗（CRT）后慢性心力衰竭患者（CHF）心脏运动同步性的变化,探讨CRT逆重构组与非逆重构组同步性的获益情况。方法：连续选择CRT术后6月以上的患者46例,根据左室收缩末容积减小≥15%分为逆重构组和非逆重构组。分别于起搏器关闭前及关闭后10分钟超声心动图检查房室间延迟（AVD）、心室间延迟（IVD）、2节段径向应变达峰时间标准差（PTrs-12SD）、12节段环向应变达峰时间标准差（PTcs-12SD）及16节段纵向应变达峰时间标准差（PTls-16SD）,比较起搏器关闭前后上述参数的变化。结果：两组患者中断CRT 10分钟后AVD均减小（非逆重构组P〈0.05,逆重构组P〈0.01）,逆重构组IVD减小（P〈0.01）,非逆重构组IVD于CRT关闭后变化无统计学意义（P〉0.05）;两组患者左室内同步化参数PTcs-12SD、PTrs-12SD、PTls-16SD在中断CRT 10分钟后的变化均无统计学意义（P〉0.05）。结论：中断CRT10分钟后,两组患者房室失同步均加重,仅逆重构组心室间失同步显著恶化。提示CRT期间,两组患者均可持续获得房室同步性益处,逆重构患者可获得心室间同步性益处;中断CRT10分钟后,两组左心室内同步性均未发生显著性改变,这种无差异的现象,需要进一步研究。     

CRT_D介导室性心动过速的研究进展

心室再同步心脏转复除颤器(CRT_D)可有效改善心力衰竭(CHF)患者的运动耐量和生活质量,预防猝死,提高生存率,但CRT_D植入后由于心室激动顺序的改变,使QT间期延长、跨室壁复极离散度(TDR)增加,潜在致室性心律失常风险;且CHF患者通常存在心肌解剖改变,传导的不均一性,也为折返性心动过速的发生提供了维持的机制;而多次电击也可导致肌钙蛋白升高,引起心肌损伤,局部心肌复极离散度增加(DRVR)和QT间期延长,以及电除颤后心肌纤维化和急性细胞损伤,反复室速、室颤也会引起进行性左心功能不全、心肌细胞凋亡、恶化心律失常基质和增加心律失常易感性。CRT_D潜在致室性心律失常作用逐渐引起人们的重视,本文就近年来CRT_D致室性心律失常的电生理机制与临床防治对策等做一综述。     

CRT_D介导室性心动过速的研究进展

心室再同步心脏转复除颤器（CRT）可有效改善心力衰竭（CHF）患者的运动耐量和生活质量,预防猝死,提高生存率,但_DCHFCRTD植入后由于心室激动顺序的改变,使QT间期延长、跨室壁复极离散度（TDR）增加,潜在致室性心律失常风险;且CHF患者通常存在心肌解剖改变,传导的不均一性,也为折返性心动过速的发生提供了维持的机制;而多次电击也可导致肌钙蛋白升高,引起心肌损伤,局部心肌复极离散度增加（DRVR）和QT间期延长,以及电除颤后心肌纤维化和急性细胞损伤,反复室速、室颤也会引起进行性左心功能不全、心肌细胞凋亡、恶化心律失常基质和增加心律失常易感性。CRT_D潜在致室性心律失常作用逐渐引起人们的重视,本文就近年来CRTD致室性心律失常的电生理机制与临床防治对策等做一综述。     

Vector Selection of a Quadripolar Left Ventricular Pacing Lead Affects Acute Hemodynamic Response to Cardiac Resynchronization Therapy: A Randomized Cross-Over Trial

Background

A suboptimal left ventricular (LV) pacing site may account for non-responsiveness of patients to cardiac resynchronization therapy (CRT). The vector selection of a novel quadripolar LV pacing lead, which was mainly developed to overcome technical issues with stimulation thresholds and phrenic nerve capture, may affect hemodynamic response, and was therefore assessed in this study. (German Clinical Trials Register DRKS00000573).

Methods and Results

Hemodynamic effects of a total of 145 LVPCs (9.1 per patient) of CRT devices with a quadripolar LV lead (Quartet™, St. Jude Medical) were assessed in 16/20 consecutive patients by invasive measurement of LV+dP/dt_max at an invasively optimized AV-interval in random order. Optimal (worst) LVPCs per patient were identified as those with maximal (minimal) %change in LV+dP/dt_max (%ΔLV+dP/dt_max) as compared to a preceding baseline. LV+dP/dt_max significantly increased in all 145 LVPCs (p<0.0001 compared to baseline) with significant intraindividual differences between LVPCs (p<0.0001). Overall, CRT acutely augmented %ΔLV+dP/dt_max by 31.3% (95% CI 24%–39%) in the optimal, by 21.3% (95% CI: 15%–27%) in the worst and by 28.2% (95% CI: 21%–36%) in a default distal LVPC. This resulted in an absolute additional acute increase in %ΔLV+dP/dt_max of 10.0% (95% CI: 7%–13%) of the optimal when compared to the worst (p<0.0001), and of 3.1% (95% CI: 1%–5%) of the optimal when compared to the default distal LVPC (p<0.001). Optimal LVPCs were not programmable with a standard bipolar lead in 44% (7/16) of patients.

Conclusion

The pacing configuration of a quadripolar LV lead determinates acute hemodynamic response. Pacing in the individually optimized configuration gives rise to an additional absolute 10% increase in %ΔLV+dP/dt_max when comparing optimal and worst vectors.     

Evaluation of Global Longitudinal Strain of Left Ventricle and Regional Longitudinal Strain in the Region of Left Ventricular Leads Predicts the Response to Cardiac Resynchronization Therapy in Patients with Ischemic Heart Failure

Myocardium viability in ischemic heart failure (HF) may affect the effect of cardiac resynchronization therapy (CRT). We hypothesized that longitudinal strain of 2D-STE, which reflects myocardium viability, can predict the response to CRT in patients with ischemic HF. 2D-STE was performed in 42 patients with HF, 1 week before and 1 year after CRT. GLS, RLS, and the LV synchrony index (SI), defined as the difference in timing to peak radial strain between LV anterior septal and posterior wall in LV short axis view, were calculated. A decrease in the LV end-systolic volume (LVESV) value of ≥15 % 1 year after CRT was defined as response to CRT. Twenty-nine patients responded to CRT (CRT-R group), while 13 patients did not respond and were assigned as CRT-NR group. Pre-CRT RLS and GLS were higher, while SI is lower, in CRT-R patients compared with CRT-NR group (p < 0.001). The ROC curve revealed that RLS of ?11.5 % predicted response to CRT with sensitivity of 80.0 % and specificity of 77.9 % (AUC = 0.84, p < 0.001). Further, GLS of ?13 % predicted response to CRT with sensitivity of 73.0 % and specificity of 73.4 % (AUC = 0.79, p < 0.001). In conclusion, LV dyssynchrony, GLS, and RLS calculated by 2D-STE can predict long-term response to CRT in patients with ischemic HF.     

心脏彩超评估高血压左心室肥厚伴左心衰竭患者心功能的临床价值及与NYHA分级的关系研究

目的:探讨心脏彩超评估高血压左心室肥厚(LVH)伴左心衰竭患者心功能的临床价值,分析其超声指标与美国纽约心脏病协会(NYHA)分级的相关性。方法:选择2017年5月至2018年5月我院收治的127例高血压LVH伴左心衰竭患者为观察组,根据NYHA分级将其分为NYHAⅡ级组(41例)、Ⅲ级组(47例)、Ⅳ级组(39例),另选择100例体检的健康志愿者为对照组。所有受试者均接受心脏彩超获得相关参数[左心房内径(LAD)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室短轴缩短率(LVFS)、左心室后壁厚度(LVPWT)、室间隔厚度(IVST)、左心室射血分数(LVEF)、左心室舒张早期充盈峰最大充盈速度/舒张晚期充盈峰最大峰值速度(E/A)比值、Tei指数],分析心脏彩超相关参数与NYHA分级之间相关性。结果:观察组患者LAD、LVEDD、LVESD、LVPWT、IVST、Tei指数高于对照组(P0.05),LVFS、LVEF、E/A比值低于对照组(P0.05)。Tei指数随着NYHA分级增高而增高(P0.05),LVFS、LVEF、E/A比值随着NYHA分级增高而降低(P0.05)。Spearman秩相关分析结果显示,Tei指数与NYHA分级呈正相关(rs=0.398,P0.05),LVFS、LVEF、E/A比值与NYHA分级呈负相关(rs=-0.285,-0.442,-0.305,P0.05)。结论:高血压LVH伴左心衰竭患者发生明显左室肥厚和左心功能降低,心脏彩超可准确评估高血压LVH伴左心衰竭患者的心功能和病情严重程度,且部分心脏彩超相关参数与NYHA分级相关。     

Role of Right Ventricular Global Longitudinal Strain in Predicting Early and Long-Term Mortality in Cardiac Resynchronization Therapy Patients

Background

Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT.

Design

We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months.

Results

RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0–12.8) vs. 19.5 (15.0–23.9) %, p<0.0001] and RVFWS (RV free wall strain) [15.6 (10.0–19.3) vs. 17.4 (10.5–22.2) %, p = 0.04], improved 6 months after CRT implantation. Increasing baseline RVGLS and RVFWS predicted survival independent of other parameters at 6 months [hazard ratio (HR) = 0.37 (0.15–0.90), p = 0.02 and HR = 0.42 (0.19–0.89), p = 0.02; per 1 standard deviation increase, respectively]. RVGLS proved to be a significant independent predictor of mortality at 24 months [HR = 0.53 (0.32–0.86), p = 0.01], and RVFWS showed a strong tendency [HR = 0.64 (0.40–1.00), p = 0.05]. The 24-month survival was significantly impaired in patients with RVGLS below 10.04% before CRT implantation [area under the curve = 0.72 (0.60–0.84), p = 0.002, log-rank p = 0.0008; HR = 5.23 (1.76–15.48), p = 0.003].

Conclusions

Our findings indicate that baseline RV dysfunction is associated with poor short-term and long-term prognosis after CRT implantation.     

The Value of Myocardial Torsion and Aneurysm Volume for Evaluating Cardiac Function in Rabbit with Left Ventricular Aneurysm

Objective

This study aimed to investigate the effect of left ventricular aneurysm (LVA) volume and left ventricular global torsion on cardiac function by real time three-dimensional echocardiography (RT-3DE) and two-dimensional speckle tracking imaging(2D-STI), to determine the accuracy of RT-3DE and 2D-STI in assessing LV function.

Methods

Thirty New Zealand rabbit models of with LVA were prepared by ligation of the middle segment of the left anterior descending and left circumflex arteries. Four weeks post-procedure, RT-3DE was conducted to obtain data on LVEF, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and LVA volume (LVAV), Peak rotation angles at the mitral valve annulus level (MV-ROT), peak rotation angles at the apical level (AP-ROT), and left ventricular global torsion angles (LV-TOR) were measured by 2D-STI.

Results

Compared with controls, LVEDV and LVESV were significantly increased in the LVA group, while LVEF, MV-ROT, AP-ROT, and LV-TOR were consistently reduced (p<0.01). Moreover, LVEF correlated with LVA volume and LV torsion angle (r= -0.778 and 0.821, p<0.01). LVA volume/LVEDV had the strongest inverse relationship with LVEF (r= -0.911, p<0.01).

Conclusion

LVA volume, LVA volume/LVEDV, and LV torsion may be used as an indicator for evaluation of cardiac function after LVA. Moreover, LVA volume/LVEDV may be a more sensitive and reliable marker of cardiac function after LVA formation.     

Ghrelin对心肌梗死大鼠恶性心律失常和早期左室重构的影响(英文)

目的:本文主要研究ghrelin对心肌梗死大鼠恶性心律失常和早期左室重构的影响。方法:心肌梗死大鼠模型每天两次注射ghrelin(100μg/kg)或生理盐水。通过超声心动图评估大鼠的心脏重量并且观察大鼠的血流动力学。使用酶免疫分析法测定血清胰岛素生长因子I(IGF-1)、血浆肾上腺素、去甲肾上腺素和多巴胺的浓度。注射药物前后分析大鼠的神经功能。结果:与对照组相比,ghrelin治疗的心肌梗死模型大鼠生存率显著增加(P0.05),心脏功能增强,但心肌梗死面积差异不大(P0.05)。结论:Ghrelin能够提高心肌梗死模型大鼠的生存率、缓解心肌梗死大鼠心率失常、改善心肌梗死大鼠左心室重构。     

Phospho‐Proteomic Analysis of Cardiac Dyssynchrony and Resynchronization Therapy

Cardiac dyssynchrony arises from conduction abnormalities during heart failure and worsens morbidity and mortality. Cardiac resynchronization therapy (CRT) re‐coordinates contraction using bi‐ventricular pacing, but the cellular and molecular mechanisms involved remain largely unknown. The aim is to determine how dyssynchronous heart failure (HF_dys) alters the phospho‐proteome and how CRT interacts with this unique phospho‐proteome by analyzing Ser/Thr and Tyr phosphorylation. Phospho‐enriched myocardium from dog models of Control, HF_dys, and CRT is analyzed via MS. There were 209 regulated phospho‐sites among 1761 identified sites. Compared to Con and CRT, HF_dys is hyper‐phosphorylated and tyrosine phosphorylation is more likely to be involved in signaling that increased with HF_dys and was exacerbated by CRT. For each regulated site, the most‐likely targeting‐kinase is predicted, and CK2 is highly specific for sites that are “fixed” by CRT, suggesting activation of CK2 signaling occurs in HF_dys that is reversed by CRT, which is supported by western blot analysis. These data elucidate signaling networks and kinases that may be involved and deserve further study. Importantly, a possible role for CK2 modulation in CRT has been identified. This may be harnessed in the future therapeutically to compliment CRT, improving its clinical effects.     

Long-Term Performance of Modern Coronary Sinus Leads in Cardiac Resynchronization Therapy

Background

Cardiac resynchronization therapy (CRT) has become an important pillar of contemporary heart failure therapy. The efficacy of CRT, however, critically relies on proper LV lead placement and performance, which is why data regarding the long-term performance of CS leads are of considerable interest. Available studies are limited by a restricted variety of lead vendors, earlier lead models and / or very short follow-up periods. In the current study, we therefore investigated the long-term performance of modern LV leads in a large "real world" cohort of patients undergoing CRT implantation.

Methods and Results

All 193 patients who had successfullyundergone CRT implantation at the University Hospital Zurich between September 2003 and January 2010 were included in the study. An overall stable course of stimulation energy was observed over time; neither ischemic etiology, lead configuration, or severely reduced EF had an influence on the evolution of energy thresholds over time. Interestingly, patients with a high energy threshold at baseline experienced a significant reduction during follow-up. In contrast, a significant drop in impedance was seen following implantation, followed by a steady course for the rest of the observation period. Only 15 patients (9.7%) showed an impedance > 1000 Ohm at any time during their follow-up. Seven lead dislocations were observed during follow up.

Conclusion

The current comprehensive analysis of long-term performance of modern coronary sinus leads demonstrates excellent stability, performance and safety. These data may have important implications for physicians involved in biventricular pacemaker implantations and in the follow-up care of these patients.     

Phenotyping of Left and Right Ventricular Function in Mouse Models of Compensated Hypertrophy and Heart Failure with Cardiac MRI

Background

Left ventricular (LV) and right ventricular (RV) function have an important impact on symptom occurrence, disease progression and exercise tolerance in pressure overload-induced heart failure, but particularly RV functional changes are not well described in the relevant aortic banding mouse model. Therefore, we quantified time-dependent alterations in the ventricular morphology and function in two models of hypertrophy and heart failure and we studied the relationship between RV and LV function during the transition from hypertrophy to heart failure.

Methods

MRI was used to quantify RV and LV function and morphology in healthy (n = 4) and sham operated (n = 3) C57BL/6 mice, and animals with a mild (n = 5) and a severe aortic constriction (n = 10).

Results

Mice subjected to a mild constriction showed increased LV mass (P<0.01) and depressed LV ejection fraction (EF) (P<0.05) as compared to controls, but had similar RVEF (P>0.05). Animals with a severe constriction progressively developed LV hypertrophy (P<0.001), depressed LVEF (P<0.001), followed by a declining RVEF (P<0.001) and the development of pulmonary remodeling, as compared to controls during a 10-week follow-up. Myocardial strain, as a measure for local cardiac function, decreased in mice with a severe constriction compared to controls (P<0.05).

Conclusions

Relevant changes in mouse RV and LV function following an aortic constriction could be quantified using MRI. The well-controlled models described here open opportunities to assess the added value of new MRI techniques for the diagnosis of heart failure and to study the impact of new therapeutic strategies on disease progression and symptom occurrence.     

Reduced Incidence of Cardiac Arrhythmias in Walkers and Runners

Purpose

Walking is purported to reduce the risk of atrial fibrillation by 48%, whereas jogging is purported to increase its risk by 53%, suggesting a strong anti-arrhythmic benefit of walking over running. The purpose of these analyses is to compare incident self-reported physician-diagnosed cardiac arrhythmia to baseline energy expenditure (metabolic equivalent hours per day, METhr/d) from walking, running and other exercise.

Methods

Proportional hazards analysis of 14,734 walkers and 32,073 runners.

Results

There were 1,060 incident cardiac arrhythmias (412 walkers, 648 runners) during 6.2 years of follow-up. The risk for incident cardiac arrhythmias declined 4.4% per baseline METhr/d walked by the walkers, or running in the runners (P = 0.0001). Specifically, the risk declined 14.2% (hazard ratio: 0.858) for 1.8 to 3.6 METhr/d, 26.5% for 3.6 to 5.4 METhr/d, and 31.7% for ≥5.4 METhr/d, relative to <1.8 METhr/d. The risk reduction per METhr/d was significantly greater for walking than running (P<0.01), but only because walkers were at 34% greater risk than runners who fell below contemporary physical activity guideline recommendations; otherwise the walkers and runners had similar risks for cardiac arrhythmias. Cardiac arrhythmias were unrelated to walking and running intensity, and unrelated to marathon participation and performance.

Conclusions

The risk for cardiac arrhythmias was similar in walkers and runners who expended comparable METhr/d during structured exercise. We found no significant risk increase for self-reported cardiac arrhythmias associated with running distance, exercise intensity, or marathon participation. Rhythm abnormalities were based on self-report, precluding definitive categorization of the nature of the rhythm disturbance. However, even if the runners’ arrhythmias include sinus bradycardia due to running itself, there was no increase in arrhythmias with greater running distance.     

改良大鼠左心室插管术及心衰大鼠左心功能指标的测定

目的完善大鼠左心室插管技术并确定充血性心力衰竭（CHF）大鼠心功能指标参数。方法将80只成年雄性SD大鼠随机分为2组：假手术组（SH）,腹主动脉缩窄模型组（CAA）。采用腹主动脉部分缩窄法制作CHF大鼠模型,BL-420E＋生物信号采集系统测定心功能参数。观察比较2组大鼠第6周后测定的心功能的各项指标。结果（1）经进一步完善大鼠左心室插管技术,成功率明显提高。（2）CAA组大鼠心功能明显减低,左室重量指数（LVMI）、左室舒张末压（LVEDP）升高,左心室内压上升、下降的最大变化速率（±dp/dtmax）下降（P〈0.01）。结论改良大鼠左心室插管术提高成功率,心衰大鼠的心功能指标明显改变。     

Indirect Measurement of Left Ventricular Function During Exercise

The electrocardiogram, phonocardiogram and carotid pulse curve were recorded during increasing work loads on an electrically braked bicycle. Heart rate increased linearly with increasing work loads while total systole and tension period decreased. In contrast, during the first periods of light work, systolic ejection time increased. As work load increased, the ejection period also decreased. The findings were interpreted as indicating an early increase in stroke volume with exercise and a later increase in the velocity of ejection.     

Volumetric Response beyond Six Months of Cardiac Resynchronization Therapy and Clinical Outcome

AimsResponse to cardiac resynchronization therapy (CRT) is often assessed six months after implantation. Our objective was to assess the number of patients changing from responder to non-responder between six and 14 months, so-called late non-responders, and compare them to patients who were responder both at six and 14 months, so-called stable responders. Furthermore, we assessed predictive values of six and 14-month response concerning clinical outcome.Methods105 patients eligible for CRT were enrolled. Clinical, laboratory, ECG, and echocardiographic parameters and patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were assessed before, and six and 14 months after implantation. Response was defined as ≥15% LVESV decrease as compared to baseline. Major adverse cardiac events (MACE) were registered until 24 months after implantation. Predictive values of six and 14-month response for MACE were examined.ResultsIn total, 75 (71%) patients were six-month responders of which 12 (16%) patients became late non-responder. At baseline, late non-responders more often had ischemic cardiomyopathy and atrial fibrillation, higher BNP and less dyssynchrony compared to stable responders. At six months, late non-responders showed significantly less LVESV decrease, and higher creatinine levels. Mean KCCQ scores of late non-responders were lower than those of stable responders at every time point, with the difference being significant at 14 months. The 14 months response was a better predictor of MACE than six months response.ConclusionsThe assessment of treatment outcomes after six months of CRT could be premature and response rates beyond might better correlate to long-term clinical outcome.     

Balloon Venoplasty of Subclavian Vein and Brachiocephalic Junction to Enable Left Ventricular Lead Placement for Cardiac Resynchronisation Therapy

This report describes the successful implantation of a LV lead using balloon venoplasty to overcome a very tight stenosis of the right subclavian vein / brachiocephalic junction for cardiac resynchronisation therapy (CRT-P) in a patient with a right sided CRT-P system and a failed epicardial LV lead. It is important for device implanters to be familiar with interventional equipments and techniques such as balloon venoplasty to overcome difficult venous access.     

超声心动图评价左室舒张性心力衰竭患者左心形态及舒张功能的应用价值

目的:研究超声心动图对左室舒张性心力衰竭(LVDHF)患者左心形态及舒张功能的评估价值。方法:选择2014年3月至2016年3月我院收治的LVDHF患者78例记为观察组,另选择同期健康志愿者80例记为对照组,两组受试者均进行血压、心率检查,并利用超声心动图技术检测两组受试者的心脏相关指标。结果:观察组的舒张压(DBP)、收缩压(SBP)、心率(HR)、左房内径(LAD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、综合指标(E/Ea)及反向血流速度(Ar)水平均明显高于对照组,而早、晚期的运动速度比(Ea/Aa)、血流传播速度(Vp)及峰速比(S/D)水平明显低于对照组,差异均有统计学意义(P0.05)。结论:超声心动图能准确地反应LVDHF患者的左心形态以及舒张功能,可在临床进行推广。