Cardiac Resynchronization Therapy Device Implantation Research Articles

Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy

BackgroundRecent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes. ObjectivesThe aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (−) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance. MethodsClinical events were quantified in patients with NICM who were +MWF (n = 68) or −MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation. ResultsIn the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for −MWF). In separate analyses of +MWF and −MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in −MWF. ConclusionsIn patients with NICM, CRT-D was superior to CRT-P in +MWF but not −MWF. These findings have implications for the choice of device therapy in patients with NICM.

Three-dimensional interlead distance predicts response and outcomes after cardiac resynchronization therapy

Approximately one-third of patients do not respond favourably to cardiac resynchronization therapy (CRT). A longer distance between ventricular leads may improve response. To study the impact of the true three-dimensional interlead distance (ILD) on outcomes. Consecutive patients undergoing CRT device implantation were included prospectively. Interlead separation was measured from postprocedural anterior-posterior and lateral chest X-rays. The three-dimensional ILD was calculated using the Pythagorean theorem. Response to CRT was defined using a composite clinical score at 6 months. Forty-two patients were included (mean age 70±9 years; QRS duration 154±31ms; left ventricular ejection fraction 26±7%; 50% ischaemic). At 6 months, 71% of patients were considered to be responders. Responders had a significantly longer ILD (108±17 vs. 87±21mm; P=0.002). When the ILD was corrected for cardiac size, the optimal cut-off value was ≥ 0.53 for predicting response (sensitivity 83%, specificity 75%, area under the curve 0.84; P=0.0002). Similar results were obtained in a historical retrospective cohort. The use of proximal electrodes on the left ventricular lead was associated with a longer ILD in 95% of patients, compared with more distal pacing configurations. In the total cohort of 74 patients (median follow-up, 420 days), those with an indexed ILD ≥ 0.53 had a 70% reduction in risk of hospitalization for heart failure (P=0.004). Longer three-dimensional ILD corrected for cardiac size measured on chest radiographs can accurately predict response to CRT and outcomes. This simple variable may be used to identify optimal lead placement and pacing configuration during CRT implantation.

2 Suitability of univentricular patients for cardiac resynchronisation therapy

Introduction In 2014 the Paediatric And Congenital Electrophysiology Society (PACES) and Heart Rhythm Society (HRS) published expert consensus statement regarding arrhythmia management in congenital heart disease, including Cardiac Resynchronisation Therapy (CRT) indications for adult congenital heart disease (ACHD) patients. These guidelines recommend CRT in univentricular hearts for those who have an impaired ventricle (EF ≤35%) with QRSd ≥150 ms, ventricular dilatation and NYHA II-IV[IIa, C]. Methods Retrospective analysis for EF, QRSd and NYHA status, from 211 patients with a Fontan circulation under specialist ACHD follow-up. Results Univentricular functional data was available for 94% (198, 84 CMR and 114 echo). 10 (5%) patients had EF ≤35%. QRSd was available for 91% (193). 5 (3%) had QRSd≥150 ms. 2 patients were identified with both EF ≤35% and QRSd ≥150 ms, fulfilling indications for CRT. One patient was NYHA IV, tricuspid atresia with an atriopulmonary fontan and subsequent conversion to total cavopulmonary circulation (TCPC). The second patient (NYHA II) had right atrial isomerism with pulmonary atresia and an unfenestrated TCPC. Conclusions If recent HRS CRT guidelines are applied to this large adult Fontan population there are very few candidates for CRT. Guidelines should be interpreted with caution. In virtually all cases, CRT device implantation in the adult Fontan will require a cardiac surgical approach associated with significant morbidity and mortality. The decision to implant CRT in Fontan patients is therefore complex and requires discussion in a combined ACHD electrophysiology MDT with careful consideration of patient anatomy and previous surgery

Prognostic significance of improvement in right ventricular systolic function during cardiac resynchronization therapy

Objectives There is conflicting evidence concerning the role of right ventricular (RV) systolic dysfunction in the long-term clinical outcome after cardiac resynchronization therapy (CRT). Therefore we aimed to assess evolution of RV systolic function during CRT, covariates associated with its improvement, and its impact on outcome.Methods and results All CRT device implantations (Jan 2009-Dec 2011) in our institution were reviewed. Records of 69 patients (25% female, mean age 62.8 ± 9.2 years, mean left ventricular (LV) ejection fraction 27 ± 8%) were analyzed. Baseline RV fractional area change (FAC) < 35% was present in 37 patients (54%). At one year, 24 of them (65%) improved in RV FAC. LV remodeling and mitral regurgitation were significantly associated with the likelihood of RV FAC improvement (OR 4.80, 95% CI 1.13-20.46, P = 0.034 and OR 0.32, 95% CI 0.12-0.89, P = 0.029, respectively). The composite endpoint of death or heart transplantation occurred in 23 patients (33%) over a mean follow-up of 2.8 ± 1.4 years. RV FAC at one year (HR 0.90, 95% CI 0.86-0.94, P < .001) was, independently of NYHA class and LV remodeling, associated with clinical outcome.Conclusions RV systolic function might improve during CRT. This seems mainly due to changed left-sided hemodynamics and LV remodeling. Good RV systolic function is independently related with better outcome.

Implantation of cardiac resynchronization therapy devices using three leads by cephalic vein dissection approach.

Percutaneous subclavian, axillary, and cephalic vein access are all used in conjunction for atrial and ventricular lead implantation, though no standard approach for cardiac resynchronization therapy (CRT) device implantation has been established. We describe an effective and a safe technique for implanting three leads via cephalic vein for CRT pacemaker and/or defibrillator implantations. A total of 171 consecutive patients undergoing de novo implantation of CRT pacemaker or defibrillator were included. Cephalic vein access was achieved by dissection and direct visualization. If the cephalic vein was inadequate, alternate means of access was determined after outset of the procedure. Procedural success rates and complications were recorded. Of the 171 de novo CRT implant attempts, 169 (98.8%) patients had successful implantation of all 3 leads on the first attempt. Of the 171 procedural attempts, 150 (87.7%) patients had all 3 leads placed via cephalic vein. Overall, complications occurred in 6 of 171 patients (3.5%) including initial and repeat procedures. These complications included seven lead dislodgements, two cases of diaphragmatic stimulation requiring lead revision, and one coronary sinus dissection without pericardial effusion. There were no cases of pneumothorax, pocket haematoma requiring evacuation, or infection. The triple lead via cephalic vein technique is safe and effective when used as a first approach for CRT device implantation.

Improvement in left ventricular intrinsic dyssynchrony with cardiac resynchronization therapy.

Objective:Cardiac resynchronization therapy (CRT) has been shown to induce a structural and electrical remodeling; the data on whether left ventricle (LV) reverse remodeling is associated with restitution of intrinsic contraction pattern are unknown. In this study, we investigated the presence of improvement in left ventricular intrinsic dyssynchrony in patients with CRT.Methods:A total of 45 CRT recipients were prospectively studied. Dyssynchrony indexes including interventricular mechanical delay (IVMD) and tissue Doppler velocity opposing-wall delay (OWD) as well as QRS duration on 12-lead surface electrocardiogram were recorded before CRT device implantation. After 1 year, patients with chronic biventricular pacing were reprogramed to VVI 40 to allow the resumption of native conduction and contraction pattern. After 4–6 h of intrinsic rhythm, QRS duration and all echocardiographic measurements were recorded. Dyssynchrony was defined as IVMD >40 ms and OWD >65 ms. CRT response was defined by a ≥15% reduction in left ventricular end-systolic volume (LVESV) at a 12-month follow-up.Results:Thirty-two patients (71%) showed response to CRT. The native QRS duration reduced significantly from 150±12 ms to 138±14 ms (p<0.001), and dyssynchrony indexes showed a significant improvement only in responders. The mean OWD reduced from 86±37 ms to 50±29 ms (p<0.001), and the mean IVMD decreased from 55±22 ms to 28±22 ms (p<0.001) in responders. The reduction in LVESV was significantly correlated with ΔOWD (r=0.47, p=0.001), ΔIVMD (r=0.45, p=0.001), and ΔQRS (r=0.34, p=0.022).Conclusion:Chronic CRT significantly improves LV native contraction pattern and causes reverse remodeling in dyssynchrony.

Safety of continuing warfarin therapy in patients undergoing cardiac resynchronization therapy device implantation

Background: Continuing warfarin therapy is considered safe for patient undergoing pacemaker or implantable cardioverter defibrillator procedures, but less evidence exists for patients undergoing cardiac resynchronization therapy (CRT) device implantation. Subjects and Methods: We retrospectively evaluated 136 consecutive patients who received a CRT device. Three periprocedural anticoagulation strategies were utilized: Group 1, continuation of therapeutic warfarin; Group 2, cessation of warfarin with heparin bridging; and Group 3, cessation of anticoagulation temporarily. Groups were compared on the incidence of complications. Results: Of the 136 patients, 87 (64%) were in Group 1, 18 (13%) were in Group 2, and 31 (23%) were in Group 3. Group 1 patients had an international normalized ratio of 2.3 ± 0.5, which was significantly higher than the other two groups. Coronary sinus dissection occurred in four patients: Three in Group 1 and one in Group 2, but no patient experienced pericardial effusion or tamponade. Group 2 experienced a higher incidence of pocket hematoma (P = 0.0065) and a longer length of hospital stay (P = 0.0069) than Group 1. Transient ischemic attack occurred in one patient in Group 3. Conclusion: Continuing warfarin with therapeutic international normalized ratio seems to be safe in individuals undergoing CRT device implantation.

Cardiac Resynchronization Therapy Device Implantation in a Patient with Cardiogenic Shock under Percutaneous Mechanical Circulatory Support.

65-year-old woman was admitted to our hospital with acute decompensated heart failure with reduced left ventricular ejection fraction and severe mitral regurgitation. Electrocardiography revealed a typical left bundle branch block and atrial fibrillation. Her condition deteriorated despite administering high-doses of inotropes and vasopressors. Pending a decision to therapy, venoarterial extracorporeal membrane oxygenation (ECMO) was performed when the patient underwent a cardiogenic shock. Although the hemodynamic status stabilized with ECMO support, weaning the patient from ECMO was not possible. Thus, we decided to perform cardiac resynchronization with defibrillator implantation as a “rescue” therapy. Five days post-implantation, the patient was successfully weaned from ECMO.

Interaction of Left Ventricular Remodeling and Regional Dyssynchrony on Long-Term Prognosis after Cardiac Resynchronization Therapy

Left ventricular (LV) remodeling in heart failure (HF) manifested by chamber dilatation is associated with worse clinical outcomes. However, the impact of LV dilatation on the association of measures of dyssynchrony with long-term prognosis and resynchronization potential after cardiac resynchronization therapy (CRT) remains unclear. Two hundred sixty CRT patients in New York Heart Association classes II to IV, with ejection fractions≤35% and QRS intervals≥120msec, were prospectively studied. Quantitative echocardiographic assessment of LV volumes and mechanical dyssynchrony by radial strain was conducted at both baseline and 6-month follow-up. Primary outcome events were predefined as death or HF hospitalization, and secondary outcome events were defined as all-cause death over the 4years after CRT. Patients were divided into two groups using the median of the baseline indexed LV end-diastolic volume (EDVI). Patients with less dilated left ventricles (EDVI<90mL/m2) had improved prognosis compared to those with severely dilated left ventricles (EDVI≥90mL/m2) for both primary (adjusted hazard ratio [HR], 2.20; 95% CI, 1.44-3.38; P<.01) and secondary (adjusted HR, 1.94; 95% CI, 1.21-3.11; P<.01) events. Similarly, reduction in baseline dyssynchrony was associated with good prognosis for both the primary (HR, 0.39; 95% CI, 0.23-0.68; P=.001) and secondary (HR, 0.41; 95% CI, 0.22-0.75; P=.004) events. A linear association was found between each 10% reduction in dyssynchrony and events (P<.01). Notably, patients with less dilated left ventricles had nearly fourfold more frequent improvement in dyssynchrony compared to those with severely dilated left ventricles (odds ratio, 4.10; 95% CI, 1.81-9.28; P<.01). No other baseline prognostic marker was associated with the resynchronization ability of CRT. Patients with severe LV remodeling (EDVI≥90mL/m2) have a poor prognosis following CRT device implantation. This is most likely due to impaired resynchronization efficacy.

Role of low‑dose dobutamine echocardiography in predicting response to biventricular pacing. Results from themulticenter Viability in Cardiac Resynchronisation Therapy (ViaCRT) study.

INTRODUCTION The response to Cardiac Resynchronisation Therapy (CRT) varies significantly, resulting in lack of improvement among the substantial patients proportion. OBJECTIVES To identify mechanical dyssynchrony indices with combination of myocardial viability characteristics for predicting long-term response to CRT. PATIENTS AND METHODS ViaCRT was a multicentre study coordinated by the Working Group on Echocardiography of Polish Cardiac Society. 127 patients with heart failure were assessed prospectively. Cardiac dyssynchrony indices and low-dose dobutamine response were determined by echocardiography prior to CRT. Improvement in Wall Motion Score Index (WMSI) or LVEF exceeding 20% at peak stress identified preserved contractile reserve. RESULTS After 12 months there was significantly different survival between subsets with and without viability characterised by WMSI decrease, corresponding to 1 (4.4%) and 20 (19.4%) fatal events respectively (p=0.048). The predictive value of LVEF gain at Dobutamine Stress Echocardiography (DSE) study was only significant at 6 months, with all-cause death occurring in 1 (1.6%) and 7 (12.1%) of patients with viable and non-viable myocardium respectively (p=0.029). Multivariate regression analysis identified the presence of septal flash and interventricular dyssynchrony as independent indices with the ability to predict echocardiographic response alone at 12 months. CONCLUSIONS The study demonstrated a significant relationship between left ventricular contractile reserve at DSE and long-term all-cause mortality following CRT device implantation. Conversely, the presence of septal flash and interventricular dyssynchrony but not myocardial viability were predictive of the response to resynchronisation. The results indicate that interference of multiple different mechanisms may be responsible for the general effect following CRT.

Coronary sinus activation patterns in patients with and without left bundle branch block undergoing electroanatomic mapping system–guided cardiac resynchronization therapy device implantation

Implantation of the left ventricular (LV) lead in segments with delayed electrical activation may improve response to cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate the amount and regional distribution of LV electrical delay (LVED) in patients with or without left bundle branch block (LBBB). We enrolled 60 patients who underwent electroanatomic mapping system-guided CRT device implantation. Activation mapping of the coronary sinus (CS) branches was performed using an insulated guidewire. LVED was defined as the interval between the beginning of the QRS complex on the surface electrocardiogram (ECG) and the local electrogram and expressed in milliseconds or as percentage of the total QRS duration (LVED%). Forty-three patients showed a LBBB and 17 a non-LBBB electrocardiographic pattern. A total of 148 CS branches (mean 2.5 per patient; range 2-4 per patient) were mapped. Patients with LBBB showed higher maximum LVED (135 ms [108-150 ms] vs 100 ms [103-110 ms]; P < .001) and LVED% (86% [79%-89%] vs 72% [54%-80%]; P < .001) than did patients without LBBB. The maximum LVED was recorded in mid-basal anterolateral or inferolateral LV segments (traditional CRT targets), significantly more often in patients with LBBB than in patients without LBBB (85% vs 59%; P = .02). The number of CS branches showing LVED >50% of the total QRS duration, >75% of the total QRS duration, and >85 ms was significantly higher in patients with LBBB than in patients without LBBB. Patients without LBBB showed lower LVED and more heterogeneous electrical activation of the CS than did patients with LBBB. This finding may contribute to a lower rate of response to CRT of patients without LBBB and suggests the use of activation mapping to guide LV lead placement.

Meta-Analysis of the Usefulness of Change in QRS Width to Predict Response to Cardiac Resynchronization Therapy

The existing data regarding the role of QRS duration (QRSd) change on cardiac resynchronization therapy (CRT) response show some inconsistent results. We conducted a meta-analysis of data obtained from observational studies to examine the impact of QRS change after CRT device implantation on the clinical and/or echocardiographic response. We searched the PubMed and EMBASE databases for relevant studies published before January 2016. Twenty-seven studies were retrieved for detailed evaluation of which 12studies with a total population of 1,545 patients met our eligibility criteria. The analysis demonstrated that QRSd narrowing was a positive predictor of response to CRT (mean difference [MD]=-19.24ms, 95% CI=-24.00 to-14.48ms, p <0.00001). Thiseffectwas consistent in the studies using clinical criteria (MD=-19.91ms, 95% CI= -27.20to-12.62ms, p <0.00001) and in those that used echocardiographic criteria (MD=-19.51ms, 95% CI=-25.78 to-13.25ms, p <0.00001). The heterogeneity test showed moderate differences among the individual studies (I2= 42%). Subgroup analysis showed that QRSd change was more pronounced in studies having a follow-up ≤6months. We did not find significant differences in studies measuring postimplantation QRSd after a certain follow-up period compared with studies measuring QRSd immediately after CRT device implantation. Further studies should clarify the exact timing of QRSd assessments during follow-up. In conclusion, QRSd shortening after CRT device implantation is associated with a favorable clinical and echocardiographic response.

56-63: Perfusion and metabolic scintigraphy with radiolabeled fatty acid in prognosis of cardiac resynchronization therapy in patients with dilated cardiomyopathy

Purpose: To study perfusion and metabolism of the left ventricular (LV) myocardium in patients with idiopathic dilated cardiomyopathy (DCM) and to identify the scintigraphic predictors of the efficacy of cardiac resynchronization therapy (CRT). Methods: The study comprised 63 patients with DCM and severe heart failure of New York Heart Association (NYHA) class III-IV, LV ejection fraction 29,7 ± 6.4 % by echocardiography, who underwent CRT. Before CRT, all patients received gamma-scintigraphy with 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and with 123I-β-methyl-iodophenyl pentadecanoic acid (123I-BMIPP) for evaluation of myocardial perfusion and metabolism, respectively. Before CRT and six months after, all patients underwent echocardiography study to estimate cardiac hemodynamics. Results: Patients were divided into two groups six months after CRT: (1) responders - LV end systolic volume (ESV) decreased by ≥ 15% (n = 39); (2) non-responders - LV ESV decreased by < 15% (n = 24). Prior to CRT, no statistically significant differences were found between groups in hemodynamic parameters (LV ejection Fraction, LV end-diastolic volume, LV end-systolic volume), intra- and interventricular dyssynchrony. Significant difference between groups was found on the following preoperative scintigraphic parameters: size of perfusion defect (9.22 ± 5.06% and 12.5 ± 4.22%, p < 0.01), metabolic defect size (7.35 ± 4.54% and 10.92 ± 4.15%, p < 0,01). Correlation analysis demonstrated the presence of significant association (r = 0.37, p < 0.5) between the original sizes of metabolic defect and changes in the values of LVESV after the implantation of CRT device. Metabolic scintigraphy showed higher diagnostic efficacy in determination of indications for CRT compared with perfusion scintigraphy (area under ROC-curves (AUC) = 0.722 and AUC = 0.612, respectively). The best metabolic defect size threshold value of 7.35% predicted CRT efficacy with the sensitivity and specificity of 77.8% and 66.7%, respectively. The study was supported by a grant from the Russian Science Foundation (№15-15-10016). Conclusion: Data, generated by metabolic scintigraphy, may be used for the integrated prediction of CRT efficacy.

216-65: Time course and relationship between electrical remodeling of native conduction and mechanical remodelling in CRT

Purpose: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients. The relationship between changes in native conduction and left ventricular (LV) structural changes has not been well established. The purpose of the study was to clarify the time course and relationship between mechanical remodelling and electrical remodelling of native conduction in CRT patients. Methods: We prospectively included 62 patients with advanced HF (age 65±10; 50 male (81%); 25 ischaemic aetiology (44.3%); EF 27 [24–31] %;) who underwent implantation of a CRT device. Echocardiographic and ECG parameters were measured at baseline, 1, 3, 6, 9, and 12 months after implantation of CRT device. Biventricular pacing was temporary inhibited during follow-up visit to record intrinsic 12-lead ECG (QRS duration, axis, PR interval, QT/QTc). Patients with a decrease of LV end systolic volume (ESV) ≥15% were considered as responders. Results: There were a statistically significant changes in intrinsic ECG parameters (QRS duration [p = 0.005], PR interval [p = 0.001], QTc [p < 0.001]) during 12 months follow-up. Significant change of ECG parameters was already observed at 1 month after implantation (QRS duration: baseline 185 [175–194] ms vs. 1 month 180 [170–186] ms; p < 0.001). However, LV volumes decreased only after 3 months of resynchronization therapy (ESV: baseline 169 [137–211] ml vs. 3 months 140 [114–202] ml; p < 0.001) and improved further at each follow-up. Additionally, significant electrical remodelling of native conduction was observed in responder but not in nonresponder group. None of these changes of intrinsic ECG parameters during first month after CRT implantation significantly predicted CRT response in multivariate analysis. Conclusions: After CRT implantation electrical remodelling of native conduction precedes detectable LV structural changes. It seems that only with CRT induction of electrical remodelling mechanical reverse remodelling could be achieved.

56-62: Response to cardiac resynchronization: the impact of baseline autonomic nervous system function

Background: Nonresponse to cardiac resynchronization therapy (CRT) occurs in around one third of the patients. Autonomic nervous system (ANS) dysfunction in heart failure (HF) contributes to its progression and confers a dismal prognosis. Purpose: We aim to evaluate the association of baseline ANS severity dysfunction in HF with CRT response. Methods: Consecutive patients submitted to CRT device implantation, in a terciary centre were included. Pre and 6 months post-CRT device implantation echocardiography was performed to assess left ventricular ejection fraction (LVEF) and left ventricle volumes. CRT response was defined as an absolute 5% increase in LVEF, from baseline. Pre-CRT 123-i-MIBG cardiac scintigraphy with determitation of heart to mediastinum ratio early (HMRe), heart to mediastinum ratio late (HMRl) and 24h Holter monitoring with evaluation of heart rate variability, were performed for the evaluation of ANS. Results: From 121 patients were included (68.6% males and mena age 68.4 ± 12.3 years old) 30.5% presented ischemic etiology and 74.3% were in NYHA class > III. Mean LVEF pre-CRT was 26.2 ± 7.1% and 70% were considered responders by echocardiography. Mean values obtained for the ANS variables were: HMRe 1.5 ± 0.2, HMRl 1.4 ± 0.2, SDNN 124 ± 68. Logistic regression demonstrated that HMRe (OR 15.1 95% CI 1.0-25.8, p = 0.05) and HMRl (OR 17.7 95% CI 1.2-26.2, p = 0.037) were independent predictors of CRT response by echocardiography. SDNN was not statistically associated with CRT response. Conclusion: Sympathetic innervation status in heart failure pre-CRT implantation, assessed by 123-i-MIBG cardiac scintigraphy, showed to be independently associated with CRT response. This finding might improve patients selection for resynchronization therapy.

136-48: Unfavourable outcome after the upgrade of an implantable cardioverter defibrillator to cardiac resynchronization therapy

Background: Cardiac resynchronization therapy (CRT) improves survival in selected patients with heart failure (HF). As the potential survival benefit of CRT performed as an upgrade from a previously implanted cardioverter defibrillator (ICD) has not been explored, we evaluated total mortality after CRT upgrade in this context. Methods and results: A total of 31 patients (27 male, mean age:63.7 ± 9.6years) with structural heart disease underwent CRT device implantation as an upgrade of a previously implanted single or dual chamber ICD between 2004 and 2015 at our Institute. The indication for ICD implantation was prophylactic based on the MADIT II or SCD-HeFT criteria (in 13 patients) or secondary prevention after a sustained ventricular arrhythmia (in 18 patients). Mean left ventricular ejection fraction (LVEF) was 29.9 ± 7.8% and mean NYHA status was 2.4 ± 0.8 at the time of ICD implantation. No indication for CRT was present in any of these patients at the time of ICD implantation. CRT upgrade was performed after a mean follow-up of 3.9 ± 2.9 years based on the following indications: widening of the QRS complex (from 108 ± 20 to 158 ± 24 msec.) in 24, decreasing LVEF (from 41.5 ± 2.1 to 26.5 ± 2.1%) in the presence of LBBB in 2, and an increase in the need for right ventricular stimulation (burden >40%) in 5 patients. A significant reduction in the QRS width after CRT upgrade (from 160.3 ± 26 to 130.3 ± 23 msec., p < 0.001), an improvement in NYHA class (from 3.1 ± 0.8 to 2.5 ± 1.0, p = 0.16) and an increase in the mean LVEF (from 27.6 to 33.3%, p = 0.049) was observed including 4 patients (13%) who demonstrated an increase in LVEF above 10 % at the 1-year follow-up. 17/31 patients (55%) died during a mean follow-up of 19.0 ± 16.6 months after CRT upgrade. No statistically significant prognostic factor of survival was found among the patients' baseline data by using the Cox proportional hazard model.

Prognostic importance of postoperative QRS widening in patients with heart failure receiving cardiac resynchronization therapy

Landmark reports have suggested that patients with QRS widening immediately after cardiac resynchronization therapy (CRT) experienced less frequently reverse left ventricular remodeling during follow-up. We sought to investigate the relationship between postoperative QRS widening relative to baseline and mortality in a prospective cohort of heart failure patients receiving CRT. A 12-lead electrocardiogram was recorded for 237 heart failure patients (New York Heart Association class II to IV, left ventricular ejection fraction ≤35%, and QRS width ≥120 ms) before and immediately after CRT device implantation. The relationships between QRS widening, all-cause and cardiovascular mortality, and echocardiographic response to CRT were studied. During a median follow-up of 24 months, 39 patients died. Fifty patients (21%) experienced QRS widening after CRT [QRS(+) group]. During follow-up, all-cause mortality was higher in QRS(+) patients than in QRS(-) patients (36-month survival free from death 81% ± 7% vs 64% ± 16%; log rank, P = .029). After adjustment for important prognostic confounders, QRS(+) patients remained associated with an excess overall mortality (adjusted hazard ratio [HR] 2.67; 95% confidence interval 1.07-6.65; P = .035) and cardiovascular mortality (adjusted hazard ratio 3.63; 95% confidence interval 1.13-11.65; P = .03). QRS(+) patients were less frequent responders to CRT than were QRS(-) patients (20 [47%] vs 136 [83%]; P < .0001). Postoperative QRS widening relative to baseline after CRT is associated with a considerable increased mortality risk during follow-up. Whether QRS narrowing should be achieved to optimize CRT placement, and thereby increase the rate of CRT responders and improve outcome, deserves further research.

Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy.

IntroductionIncreased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects.Material and methodsThe study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits.ResultsThe HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6–3.8 vs. 2.1, IQR: 1.4–3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36–64 vs. 53. IQR 44–76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF (r = –0.5, p = 0.001) and positively with BNP (r = 0.5, p = 0.008) and CRP concentrations (r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: –0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04).ConclusionsHF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients’ functional status is associated with a smaller change of sIL-6R concentration in time.

Cardiac Resynchronization Therapy: US Trends and Disparities in Utilization and Outcomes.

The use of cardiac resynchronization therapy (CRT) has increased significantly since its initial approval in 2001 for use in patients with advanced heart failure. However, trends in utilization of CRT have not been systematically characterized. We used the Nationwide Inpatient Sample database to identify all patients with CRT implantation during 2002 to 2010. The overall trends in CRT device implantation, patient characteristics, and outcomes were examined in detail and compared among demographic subgroups. During 2002 to 2010, a total of 374,202 CRT procedures were recorded. Significant and persistent gender and racial disparities favoring men (71.4%) and white (79.6%), respectively, were noted in all years. The highest number of CRT devices were implanted in the 65- to 84-year age group (64.6%), with significant increase in number of CRT implants in older patients ≥ 85 years over the years (P = 0.02). The CRT-associated in-hospital mortality improved from 1.08% in 2003 to 0.70% in 2010 (P = 0.03). The correlates of higher mortality included males (0.93% versus 0.71% in females; P = 0.04) and older age (age ≥ 85 years had 1.5% mortality versus 0.8% for age < 85 year; P < 0.001). The mean hospital length of stay for CRT decreased, while mean CRT-associated hospital charges increased progressively over the years. Factors associated with higher charges were gender (males > females), older age, and greater comorbidities. CRT implantation is a relatively safe procedure that has become safer in higher risk patients. However, significant disparities in CRT utilization exist in certain demographic subgroups, and these disparities have persisted across the years.

Electrocardiographic correlates of mechanical dyssynchrony in recipients of cardiac resynchronization therapy devices

The relationship between electrical and mechanical indices of cardiac dyssynchronization in systolic heart failure (HF) remains poorly understood. We examined retrospectively this relationship by using the daily practice tools in cardiology in recipients of cardiac resynchronization therapy (CRT) systems. We studied 119 consecutive patients in sinus rhythm and QRS ≥ 120 ms (mean: 160 ± 17 ms) undergoing CRT device implantation. P wave duration, PR, ePR (end of P wave to QRS onset), QT, RR-QT, JT and QRS axis and morphology were putative predictors of atrioventricular (diastolic filling time [DFT]/RR), interventricular mechanical dyssynchrony (IVMD) and left intraventricular mechanical dyssynchrony (left ventricular pre-ejection interval [PEI] and other measures) assessed by transthoracic echocardiography (TTE). Correlations between TTE and electrocardiographic measurements were examined by linear regression. Statistically significant but relatively weak correlations were found between heart rate (r=-0.5), JT (r=0.3), QT (r=0.3), RR-QT intervals (r=0.5) and DFT/RR, though not with PR and QRS intervals. Weak correlations were found between: (a) QRS (r=0.3) and QT interval (r=0.3) and (b) IVMD > 40 ms; and between (a) ePR (r=-0.2), QRS (r=0.4), QT interval (r=0.3) and (b) LVPEI, though not with other indices of intraventricular dyssynchrony. The correlations between electrical and the evaluated mechanical indices of cardiac dyssynchrony were generally weak in heart failure candidates for CRT. These data may help to explain the discordance between electrocardiographic and echocardiographic criteria of ventricular dyssynchrony in predicting the effect of CRT.