Patient-reported health status prior to cardiac resynchronisation therapy identifies patients at risk for poor survival and prolonged hospital stays

Background

Patient-reported factors have largely been neglected in search of predictors of response to cardiac resynchronisation therapy (CRT). The current study aimed to examine the independent value of pre-implantation patient-reported health status in predicting four-year survival and cardiac-related hospitalisation of CRT patients.

Methods

Consecutive patients (N = 139) indicated to receive a first-time CRT-defibrillator at the University Medical Center Utrecht were asked to complete a set of questionnaires prior to implantation. The Kansas City Cardiomyopathy Questionnaire (KCCQ) was used to assess heart failure-specific health status. Data on patients’ demographic, clinical and psychological characteristics at baseline, and on cardiac-related hospitalisations and all-cause deaths during a median follow-up of 3.9 years were obtained from purpose-designed questionnaires and patients’ medical records.

Results

Results of multivariable Cox regression analyses showed that poor patient-reported health status (KCCQ score < 50) prior to implantation was associated with a 2.5-fold increased risk of cardiac hospitalisation or all-cause death, independent of sociodemographic, clinical and psychological risk factors (adjusted hazard ratio 2.46, 95 % confidence interval (CI) 1.30–4.65). Poor health status was not significantly associated with the absolute number of cardiac-related hospital admissions, but with the total number of days spent in hospital during follow-up (adjusted incidence rate ratio 3.20, 95 % CI 1.88–5.44).

Conclusions

Patient-reported health status assessed prior to CRT identifies patients at risk for poor survival and prolonged hospital stays, independent of traditional risk factors. These results emphasise the importance of incorporating health status measures in cardiovascular research and patient management. Heart failure patients reporting poor health status should be identified and offered appropriate additional treatment programs.     

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.     

Cardiac resynchronisation therapy in patients with left bundle branch block with residual conduction

AimTo evaluate whether left bundle branch block with residual conduction (rLBBB) is associated with worse outcomes after cardiac resynchronisation therapy (CRT).MethodsAll consecutive CRT implants at our institution between 2006 and 2013 were identified from our local device registry. Pre- and post-implant patient specific data were extracted from clinical records.ResultsA total of 690 CRT implants were identified during the study period. Prior to CRT, 52.2% of patients had true left bundle branch block (LBBB), 19.1% a pacing-induced LBBB (pLBBB), 11.2% a rLBBB, 0.8% a right bundle branch block (RBBB), and 16.5% had a nonspecific intraventricular conduction delay (IVCD) electrocardiogram pattern. Mean age at implant was 67.5 years (standard deviation [SD] = 10.6), mean left ventricular ejection fraction (LV EF) was 25.7% (SD = 7.9%), and mean QRS duration was 158.4 ms (SD = 32 ms). After CRT, QRS duration was significantly reduced in the LBBB (p < 0.001), pLBBB (p < 0.001), rLBBB (p < 0.001), RBBB (p = 0.04), and IVCD groups (p = 0.03). LV EF significantly improved in the LBBB (p < 0.001), rLBBB (p = 0.002), and pLBBB (p < 0.001) groups, but the RBBB and IVCD groups showed no improvement. There was no significant difference in mortality between the LBBB and rLBBB groups. LV EF post-CRT, chronic kidney disease, hyperkalaemia, hypernatremia, and age at implant were significant predictors of mortality.ConclusionCRT in patients with rLBBB results in improved LV EF and similar mortality rates to CRT patients with complete LBBB. Predictors of mortality post-CRT include post-CRT LV EF, presence of CKD, hyperkalaemia, hypernatremia, and older age at implant.     

Cardiac resynchronisation therapy and the role of optimal device utilisation

Despite established selection criteria, 30 to 40% of patients do not respond to cardiac resynchronisation therapy. By optimising programming of the device response to cardiac resynchronisation, therapy can be improved. (Neth Heart J 2009;17:354–7.)     

Cardiac resynchronisation therapy: results from daily practice in Rijnstate Hospital, Arnhem

BackgroundCardiac resynchronisation therapy (CRT) is an effective treatment to improve the clinical outcome of selected patients with heart failure. Clinical trials have studied clinical outcome and reported clinical improvements, but clinical consequences and results in daily practice are less well known. We evaluated clinical outcome in all patients with CRT implantation in our centre. MethodsData of 119 consecutive patients who met the criteria for CRT implantation in Rijnstate Hospital, Arnhem in the period 28 November 2000 until 1 January 2006 were collected. We analysed implantation procedure, hospitalisation for heart failure or other causes, mortality and device-related events. ResultsIn total 119 patients (83 men, 36 women; mean age 69 years) were eligible for CRT. Before implantation they had received optimal pharmacological therapy. Implantation was successful in 97% of patients. Procedural-related complications were seen in eight patients. During follow-up, 22 patients (18.5%: 14 men, 8 women) died. Causes of death were heart failure (11 patients), sudden cardiac death (4 patients) and noncardiac death (7 patients). Hospitalisation occurred 81 times, of which 77 for cardiac reasons. In follow-up the estimated five-year cumulative survival was 70%. ConclusionThis retrospective study from a single centre showed a high procedural success rate, low prevalence of complications and low mortality in comparison to other studies. Despite better functional capacity, the hospitalisation rate due to heart failure was high. (Neth Heart J 2009;17:6-8.)     

New insights in LV torsion for the selection of cardiac resynchronisation therapy candidates

Recent literature indicates that torsion of the left ventricle (LV) is a promising predictor for response to cardiac resynchronisation therapy (CRT). Among patients with severe heart failure, 45 to 75% of patients show rigid body rotation, where the base and apex rotate in the same direction, instead of normal, opposite rotation. The occurrence of this phenomenon seems to be a good indicator for response to CRT. From this review, it can be concluded that LV torsion might be a welcome addition to current selection criteria.     

The influence of right ventricular stimulation on acute response to cardiac resynchronisation therapy

Background

The contribution of right ventricular (RV) stimulation to cardiac resynchronisation therapy (CRT) remains controversial. RV stimulation might be associated with adverse haemodynamic effects, dependent on intrinsic right bundle branch conduction, presence of scar, RV function and other factors which may partly explain non-response to CRT. This study investigates to what degree RV stimulation modulates response to biventricular (BiV) stimulation in CRT candidates and which baseline factors, assessed by cardiac magnetic resonance imaging, determine this modulation.

Methods and results

Forty-one patients (24 (59 %) males, 67 ± 10 years, QRS 153 ± 22 ms, 21 (51 %) ischaemic cardiomyopathy, left ventricular (LV) ejection fraction 25 ± 7 %), who successfully underwent temporary stimulation with pacing leads in the RV apex (RV_apex) and left ventricular posterolateral (PL) wall were included. Stroke work, assessed by a conductance catheter, was used to assess acute haemodynamic response during baseline conditions and RV_apex, PL (LV) and PL+RV_apex (BiV) stimulation.Compared with baseline, stroke work improved similarly during LV and BiV stimulation (∆+ 51 ± 42 % and ∆+ 48 ± 47 %, both p < 0.001), but individual response showed substantial differences between LV and BiV stimulation. Multivariate analysis revealed that RV ejection fraction (β = 1.01, p = 0.02) was an independent predictor for stroke work response during LV stimulation, but not for BiV stimulation. Other parameters, including atrioventricular delay and scar presence and localisation, did not predict stroke work response in CRT.

Conclusion

The haemodynamic effect of addition of RV_apex stimulation to LV stimulation differs widely among patients receiving CRT. Poor RV function is associated with poor response to LV but not BiV stimulation.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0770-x) contains supplementary material, which is available to authorized users.     

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.     

Optimisation of cardiac resynchronization therapy in clinical practice during exercise

Aims

Although cardiac resynchronisation therapy (CRT) is an established treatment to improve cardiac function, a significant amount of patients do not experience noticeable improvement in their cardiac function. Optimal timing of the delay between atrial and ventricular pacing pulses (AV delay) is of major importance for effective CRT treatment and this optimum may differ between resting and exercise conditions. In this study the feasibility of haemodynamic measurements by the non-invasive finger plethysmographic method (Nexfin) was used to optimise the AV delay during exercise.

Methods and results

Thirty-one patients implanted with a CRT device in the last 4 years participated in the study. During rest and in exercise, stroke volume (SV) was measured using the Nexfin device for several AV delays. The optimal AV delay at rest and in exercise was determined using the least squares estimates (LSE) method. Optimisation created a clinically significant improvement in SV of 10 %. The relation between HR and the optimal AV delay was patient dependent.

Conclusion

A potential increase in SV of 10 % can be achieved using Nexfin for optimisation of AV delay during exercise. A considerable number of patients showed benefit with lengthening of the AV delay during exercise.     

Visualisation of coronary venous anatomy by computed tomography angiography prior to cardiac resynchronisation therapy implantation

Background

The purpose of this study was to illustrate the additive value of computed tomography angiography (CTA) for visualisation of the coronary venous anatomy prior to cardiac resynchronisation therapy (CRT) implantation.

Methods

Eighteen patients planned for CRT implantation were prospectively included. A specific CTA protocol designed for visualisation of the coronary veins was carried out on a third-generation dual-source CT platform. Coronary veins were semi-automatically segmented to construct a 3D model. CTA-derived coronary venous anatomy was compared with intra-procedural fluoroscopic angiography (FA) in right and left anterior oblique views.

Results

Coronary venous CTA was successfully performed in all 18 patients. CRT implantation and FA were performed in 15 patients. A total of 62 veins were visualised; the number of veins per patient was 3.8 (range: 2–5). Eighty-five per cent (53/62) of the veins were visualised on both CTA and FA, while 10% (6/62) were visualised on CTA only, and 5% (3/62) on FA only. Twenty-two veins were present on the lateral or inferolateral wall; of these, 95% (21/22) were visualised by CTA. A left-sided implantation was performed in 13 patients, while a right-sided implantation was performed in the remaining 2 patients because of a persistent left-sided superior vena cava with no left innominate vein on CTA.

Conclusion

Imaging of the coronary veins by CTA using a designated protocol is technically feasible and facilitates the CRT implantation approach, potentially improving the outcome.

     

Mitotic activity in wheat shoot apical meristems: effect of dissection to expose the apical dome

An efficient method, less laborious than histological procedures, is described to screen relatively large numbers of shoot apices for mitotic activity. Mitotic activity of shoot apices of Triticum aestivum L. was observed by differential interference contrast (DIC) microscopy of apices infiltrated with a clearing fluid (chloral hydrate/phenol/lactic acid/dibutylphthalate/benzyl benzoate). Serial optical sections were viewed through entire vegetative apical domes and floral primordia. In vegetative shoots, mitotic cells were observed throughout the light and dark cycles of plants maintained in either 8 or 16 h photoperiods. Mitotic activity was lower in the dark phase and increased through the light cycle in both photoperiods. Cells in L1 and L2 layers at the summit of the apex were mitotically active and contributed to the developing shoot and floral structures. Thus, cells in L2 at the summit of vegetative apices are valid targets for transformation leading subsequently to modified germ line cells. Dissections to expose apices for DNA delivery inhibited mitotic activity; recovery periods greater than 48 h would be needed for restoration of normal activity. This suggests that a period of recovery from dissection would be beneficial for attempts at integrative transformation of apical cells.     

Identifying delayed left ventricular lateral wall activation in patients with non-specific intraventricular conduction delay using coronary venous electroanatomical mapping

Background

Delayed left ventricular (LV) lateral wall activation is considered the electrical substrate that characterises patients suitable for cardiac resynchronisation therapy (CRT). Although typically associated with left bundle branch block, delayed LV lateral wall activation may also be present in patients with non-specific intraventricular conduction delay (IVCD). We assessed LV lateral wall activation in a cohort of CRT candidates with IVCD using coronary venous electroanatomical mapping, and investigated whether baseline QRS characteristics on the ECG can identify delayed LV lateral wall activation in this group of patients.

Methods

Twenty-three consecutive CRT candidates with IVCD underwent intra-procedural coronary venous electroanatomical mapping using EnSite NavX. Electrical activation time was measured in milliseconds from QRS onset and expressed as percentage of QRS duration. LV lateral wall activation was considered delayed if maximal activation time measured at the LV lateral wall (LVLW-AT) exceeded 75 % of the QRS duration. QRS morphology, duration, fragmentation, axis deviation, and left anterior/posterior fascicular block were assessed on baseline ECGs.

Results

Delayed LV lateral wall activation occurred in 12/23 patients (maximal LVLW-AT = 133 ± 20 ms [83 ± 5 % of QRS duration]). In these patients, the latest activated region was consistently located on the basal lateral wall. QRS duration, and prevalence of QRS fragmentation and left/right axis deviation, and left anterior/posterior fascicular block did not differ between patients with and without delayed LV lateral wall activation.

Conclusion

Coronary venous electroanatomical mapping can be used at the time of CRT implantation to determine the presence of delayed LV lateral wall activation in patients with IVCD. QRS characteristics on the ECG seem unable to identify delayed LV lateral wall activation in this subgroup of patients.     

Pathophysiology of dyssynchrony: of squirrels and broken bones

The genesis of cardiac resynchronisation therapy (CRT) consists of ‘bedside’ research and ‘bench’ studies that are performed in series with each other. In this field, the bench studies are crucial for understanding the pathophysiology of dyssynchrony and resynchronisation. In a way, CRT started with the insight that abnormal ventricular conduction, as caused by right ventricular pacing, has adverse effects. Out of this research came the ground-breaking insight that ‘simple’ disturbances in impulse conduction, which were initially considered innocent, proved to result in a host of molecular and cellular derangements that lead to a vicious circle of remodelling processes that facilitate the development of heart failure. As a consequence, CRT does not only correct conduction abnormalities, but also improves myocardial properties at many levels. Interestingly, corrections by CRT do not exactly reverse the derangements, induced by dyssynchrony, but also activate novel pathways, a property that may open new avenues for the treatment of heart failure.     

早期NT-proBNP变化率对CRT患者长期预后的评价

目的:探讨慢性心力衰竭患者心脏再同步化治疗(cardiac resynchronizationtherapy,CRT)后早期血浆N末端脑钠肽前体(N-terminal pro-B-type natriureticpeptide,NT-proBNP)变化对患者长期预后评估的价值。方法:采取随机对照的方法,选取40例符合行CRT治疗的慢性心力衰竭患者,分别检测CRT植入前、CRT植入后14 d的血浆NT-proBNP水平,并计算14 d内血浆NT-proBNP水平变化率(△NT-proBNP),根据14 d△NT-proBNP结果分为A组(△NT-proBNP30%)、B组(△NT-proBNP≥30%),观察CRT植入术后1年内患者的不良心脏事件发生率、病死率、再住院时间及1年后纽约心功能(New York Heart Association,NYHA)分级、左室射血分数(Left ventricular ejection fraction,LVEF)、左室舒张末内径(left ventricular end-diastolic diameter,LVEDD)。结果:B组患者1年不良心脏事件发生率、病死率及左室舒张末内径(LVEDD)均低于A组患者,再住院时间及左室舒张末内径(LVEDD)明显短于A组患者,而NYHA心功能分级、左室射血分数(LVEF)高于A组患者(P0.05)。结论:慢性心力衰竭患者行CRT后早期NT-proBNP水平变化可以评估患者病情的长期预后。     

Influence of intrinsic myocardial conduction on paced QRS morphology during cardiac resynchronization therapy follow up

We report two cases of patients of cardiac resynchronization therapy (CRT) whose ECGs, during follow up, showed different paced QRS morphology as compared to those of immediate post-device implantation. Parameters of leads, including sensitivity and capture thresholds, were unchanged. There was no lead dislodgement confirmed on fluoroscopy. The ECGs obtained in device off mode showed different intrinsic QRS morphology as compared to those of pre-implant morphology. These changes were attributable to electrolyte imbalance in one patient and progressive intraventricular conduction defect in the other. These cases demonstrate that intrinsic myocardial conduction pattern influences paced QRS morphology. Irreversible change in paced QRS morphology may indicate poor prognosis.     

Feasibility and potential benefit of pre-procedural CMR imaging in patients with ischaemic cardiomyopathy undergoing cardiac resynchronisation therapy

Netherlands Heart Journal - To determine the feasibility and potential benefit of a&nbsp;full cardiac magnetic resonance (CMR) work-up for assessing the location of scarred myocardium and the...     

Targeting of an apical endosomal protein to endosomes in Madin-Darby canine kidney cells requires two sorting motifs

The efficient sorting and targeting of endocytosed macromolecules is critical for epithelial function. However, the distribution of endosomal compartments in these cells remains controversial. In this study, we show that polarized Madin–Darby canine kidney (MDCK) cells target the apical endosomal protein endotubin into an apical early endosomal compartment that is distinct from the apical recycling endosomes. Furthermore, through a panel of site-directed mutations we show that signals required for apical endosomal targeting of endotubin are composed of two distinct motifs on the cytoplasmic domain, a hydrophobic motif and a consensus casein kinase II site. Endotubin-positive endosomes in MDCK cells do not label with basolaterally internalized transferrin or ricin, do not contain the small guanosine triphosphate-binding protein rab11, and do not tubulate in response to low concentrations of brefeldin-A (BFA). Nevertheless, high concentrations of BFA reversibly inhibits the sorting of endotubin from transferrin and cause colocalization in tubular endosomes. These results indicate that, in polarized cells, endotubin targets into a distinct subset of apical endosomes, and the targeting information required both for polarity and endosomal targeting is provided by the cytoplasmic portion of the molecule.     

Long-term prognosis of patients with cardiac syndrome X: a review

AimsFollow-up studies of patients with cardiac syndrome X (CSX) generally report good prognosis. However, some recent studies report an adverse outcome for women.ConclusionThe present review of recent archival literature demonstrates an overall major cardiac event rate of 1.5% per 5 years. Although this is an excellent prognosis for CSX patients, the quality of life is impaired because of the high recurrence rate of angina pectoris (55%).     

Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy

Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF.