Influence of multimorbidity and socioeconomic position on long-term healthcare utilization and prognosis in patients after cardiac resynchronization therapy implantation.

Aims: We aimed to investigate the influence of socioeconomic position (SEP) and multimorbidity on cross-sectional healthcare utilization and prognosis in patients after cardiac resynchronization therapy (CRT) implantation. Methods and results: We included first-time CRT recipients with left ventricular ejection fraction ≤35% implanted between 2000 and 2017. Data on chronic conditions, use of healthcare services, and demographics were obtained from Danish national administrative and health registries. Healthcare utilization (in- and outpatient hospitalizations, activities in general practice) was compared by multimorbidity categories and SEP by using a negative binomial regression model. The association between SEP, multimorbidity, and prognostic outcomes was analysed using Cox proportional hazards regression. We followed 2007 patients (median age of 70 years), 79% were male, 75% were on early retirement or state pension, 37% were living alone, and 41% had low education level for a median of 5.2 [inter-quartile range: 2.2-7.3) years. In adjusted regression models, a higher number of chronic conditions were associated with increased healthcare utilization. Both cardiovascular and non-cardiovascular hospital contacts were increased. Patients with low SEP had a higher number of chronic conditions, but SEP had limited influence on healthcare utilization. Patients living alone and those with low educational level had a trend towards a higher risk of all-cause mortality [adjusted hazard ratio (aHR): 1.17, 95% confidence interval (CI) 1.03-1.33, and aHR 1.09, 95% CI 0.96-1.24). Conclusion: Multimorbidity increased the use of cross-sectional healthcare services, whereas low SEP had minor influence on the utilizations. Living alone and low educational level showed a trend towards a higher risk of mortality after CRT implantation.

Association between socioeconomic position and discontinuation of pharmacotherapy for heart failure after cardiac resynchronization therapy.

AIMS: Pharmacological therapy remains a cornerstone in heart failure (HF) treatment despite implantation of a cardiac resynchronization therapy (CRT) device. The aim of this study was to investigate the association between 1) drug discontinuation, and 2) long-term adherence to HF pharmacotherapy after CRT implantation and socioeconomic position and multimorbidity. METHODS AND RESULTS: We conducted a registry-based cohort study including all patients who underwent a first-time CRT implantation at Aarhus University Hospital from 2000-2017. HF pharmacotherapy included beta blockers (BBs), renin angiotensin system inhibitors (ACEI/ARB), and mineralocorticoid receptor antagonists (MRAs). Patients were identified using the Danish Pacemaker and ICD Registry, and information about medication and comorbidities was obtained through linkage to the Danish health registries. We identified 2,007 patients of whom 1,880 (94%) were eligible for inclusion. The cumulative incidence of drug discontinuation at 10 years was 6% (95% confidence interval [CI] 5-8%) for BB, 10% (95% CI 9-12%) for ACEI/ARB, and 24% (95% CI 20-27%) for MRAs. Living alone was associated with higher BB discontinuation rates (hazard ratio [HR] 1.83, 95%CI 1.20-2.79), whereas patients with multimorbidity were more likely to discontinue ACEI/ARB- (HR 1.92, 95%CI 1.33-2.80) and MRA therapy (HR 1.51, 95% CI 1.10-2.09). Income- and educational level did not influence drug discontinuation rates, and similar adherence patterns were observed across all strata of socioeconomic position and multimorbidity. CONCLUSION: In patients with CRTs, drug discontinuation rates were low, and adherence to HF pharmacotherapy was comparable regardless of socioeconomic position. Living alone and multimorbidity were associated with discontinuation of specific HF drugs.

Magnetic resonance imaging in patients with temporary external pacemakers.

AIMS: To describe safety and feasibility of magnetic resonance imaging (MRI) in patients with transvenous temporary external pacemakers and whether artefacts affect the diagnostic image quality during cardiac MRI. METHODS AND RESULTS: We reviewed records of all patients treated with temporary external pacing between 2016 and 2020 at a tertiary centre. Temporary pacing was established using a transvenous standard active fixation pacing lead inserted percutaneously and connected to a MRI-conditional pacemaker taped to the skin. All patients undergoing cardiac or non-cardiac MRI during temporary transvenous pacing were identified. Before MRI, devices were programmed according to guidelines for permanent pacemakers, and patients were monitored with continuous electrocardiogram during MRI. Of 827 consecutive patients receiving a temporary external pacemaker, a total of 44 (5%) patients underwent MRI (mean age 71 years, 13 [30%] females). Cardiac MRI was performed in 22 (50%) patients, while MRI of cerebrum, spine, and other regions was performed in the remaining patients. Median time from implantation of the temporary device to MRI was 6 (3-11) days. During MRI, we observed no device-related malfunction or arrhythmia. Nor did we detect any change in lead sensing, impedance, or pacing threshold. We observed no artefacts from the lead or pacemaker compromising the diagnostic image quality of cardiac MRI. MRI provided information to guide the clinical management in all cases. CONCLUSION: MRI is feasible and safe in patients with temporary external pacing established with a regular MRI-conditional pacemaker and a standard active fixation lead. No artefacts compromised the diagnostic image quality.

Non-infective left ventricular lead complications requiring re-intervention following cardiac resynchronization therapy: prevalence, causes and outcomes.

PURPOSE: Left ventricular (LV) lead complications in cardiac resynchronization therapy are challenging and poorly reported. We aimed to establish prevalence, causes and outcomes of LV lead complications requiring re-intervention. METHODS: We analysed the rate of complications in 2551 consecutive patients who received a transvenous de novo LV lead as part of a cardiac resynchronization therapy device between 2000 and 2018. LV lead complications requiring re-intervention were identified; those due to infection were excluded. Patient, procedural and device characteristics, and outcomes were examined for non-infective LV lead complications requiring re-intervention. RESULTS: During a median of 4.7 years, 142 (5.6%) patients required re-intervention for non-infective LV lead complications with a decrease from 10.7% between 2000 and 2004, 8.7% between 2005 and 2009, 3.2% between 2010 and 2014 to 3.2% after 2014. The most common complications were LV lead displacement (50%), high pacing threshold (28%) and phrenic nerve stimulation (15%). Of the complications, 79 (56%) occurred within 90 days post-implant and 63 (44%) later. At the end of the study period, 132/142 patients (93%) had a functional LV lead. Lead re-intervention was associated with higher risk of complications (20%), but no increase in mortality (P = 0.19). Quadripolar leads had longer longevity and lower risk of complications compared with unipolar and bipolar LV leads. CONCLUSIONS: A small but significant proportion of patients required LV lead re-intervention for complications following de novo implant. Lead displacement accounted for half of the re-interventions. Re-intervention was associated with a higher complication rate, but 92% of these patients had functional LV leads at the end of follow-up.

Left Atrial Function Determined by Cardiac Computed Tomography Predicts Device-Detected Atrial High-Rate Episodes in Patients Treated With Cardiac Resynchronization Therapy.

OBJECTIVE: The objective of this study was to examine whether left atrial (LA) volumes and function were associated with atrial high-rate episodes (AHREs) in patients with cardiac resynchronization therapy (CRT). METHODS: Ninety-two consecutive patients without prior atrial fibrillation underwent clinical evaluation, echocardiograms, and cardiac computed tomography (CT) before CRT implantation and after 6 months. Left atrial volumes and LA emptying fraction (LAEF) were derived by CT images reconstructed at 5% phase increments of the cardiac cycle. Cox regression was used to assess associations between AHRE and LA anatomical and functional variables. RESULTS: Twenty-two patients (24%) developed AHRE during 1.9 years (SD, 1 year) At baseline, higher LAEF was associated with a lower risk of AHRE (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.91-0.98; P = 0.003), and large LA minimal (LAmin) volume was related to higher risk of AHRE (HR, 1.03; 95% CI, 1.00-1.06; P = 0.04). When combining LAEF and LAmin volume, only LAEF remained associated with occurrence of AHRE. Higher passive LAEF was associated with lower risk of AHRE (HR, 0.95; 95% CI, 0.91-0.98; P = 0.003). CONCLUSIONS: In patients with CRT, low preimplant LAEF measured by cardiac CT was independently associated with device-detected AHRE.

Reproducibility of measuring QRS duration and implications for optimization of interventricular pacing delay in cardiac resynchronization therapy.

BACKGROUND: QRS narrowing after CRT is a predictor of patient outcome. Further narrowing can be obtained by interventricular pacing delay (VVd) optimization, raising interest to inter and intraobserver variation in manual measurements of QRS duration. METHODS: (a) Variation in intrinsic rhythm QRS duration in CRT patients with LBBB: In 40 intrinsic 12-lead ECGs, six observers measured QRS duration defined as widest QRS in any lead. In 20 of these ECGs, two observers repeated the measurements. (b) Variation in paced QRS duration at different VVd settings and agreement in selecting the narrowest QRS: In 20 CRT patients, five paced ECGs were recorded at different VVds. The most frequently selected VVd(s) estimated to cause the narrowest QRS in each patient defined the optimal VVd. Two observers repeated the measurements and VVd selections. RESULTS: Absolute interobserver difference in measured QRS duration in intrinsic rhythm ECGs was mean 2 ms, range (-40; 40 ms), mean limits of agreement (LoA): -21; 25 ms. Absolute interobserver difference in measured QRS duration in paced ECGs was mean 3 ms, range (-50; 60 ms), mean LoA: -20; 27 ms. There was no difference in LoA between intrinsic and paced QRS duration (lower limit p = 0.68; upper limit p = 0.44). The optimal VVd was included in 17/20 (85%) of the VVd selections by six observers. Interobserver variation was comparable with the intraobserver variation. CONCLUSIONS: Interobserver variation and intraobserver variation in manually measured paced and intrinsic rhythm QRS duration are clinically acceptable and comparable in a cohort of CRT patients. Inter and intraobserver reproducibility for selecting the optimal VVd is good and warrants manual VVd optimization for QRS narrowing in CRT.

Time until diagnosis of clinical events with different remote monitoring systems in implantable cardioverter-defibrillator patients.

BACKGROUND: Remote monitoring (RM) is an established technology integrated into routine follow-up of patients with an implantable cardioverter-defibrillator (ICD). Current RM systems differ according to transmission frequency and alert definition. OBJECTIVE: The purpose of this study was to compare the time difference between detection and acknowledgment of clinically relevant events between 4 RM systems. METHODS: We analyzed time delay between detection of ventricular arrhythmic and technical events by the ICD and acknowledgment by hospital staff in 1802 consecutive patients followed with RM between September 2014 and August 2016. Devices from Biotronik (BIO; n = 374), Boston Scientific (BSC; n = 196), Medtronic (MDT; n = 468), and St Jude Medical (SJM; n = 764) were included. We identified all events from RM web pages and their acknowledgment with RM or at in-clinic follow-up. Events that occurred during weekends were excluded. RESULTS: We included 3472 events. Proportion of events acknowledged within 24 hours was 72%, 23%, 18%, and 65% with BIO, BSC, MDT, and SJM, respectively, with median times of 13, 222, 163, and 18 hours from detection to acknowledgment (P <.001 for both comparisons between manufacturers). Including only events transmitted as alerts by RM, 72%, 68%, 61%, and 65% for BIO, BSC, MDT and SJM, respectively, were acknowledged within 24 hours. Variation in time to acknowledgment of ventricular tachyarrhythmia episodes not treated with shock therapy was the primary cause for the difference between manufacturers. CONCLUSION: Significant and clinically relevant differences in time delay from event detection to acknowledgment exist between RM systems. Varying definitions of which events RM transmits as alerts are important for the differences observed.

Left ventricular performance during triggered left ventricular pacing in patients with cardiac resynchronization therapy and left bundle branch block.

PURPOSE: To assess the acute effect of triggered left ventricular pacing (tLVp) on left ventricular performance and contraction pattern in patients with heart failure, left bundle branch block (LBBB), and cardiac resynchronization therapy (CRT). METHODS: Twenty-three patients with pre-implant QRS complex >150 ms, QRS complex narrowing under CRT, and sinus rhythm were included ≥3 months after CRT implantation. Echocardiographic assessment of left ventricular ejection fraction (LVEF), global peak systolic longitudinal strain (GLS), and contraction pattern by 2D strain was performed during intrinsic conduction, tLVp, and BiV pacing and compared as paired data. Echocardiographic analysis was done blinded with respect to pacing mode. RESULTS: LVEF was significantly higher during BiV pacing (47 ± 11 %) compared with intrinsic conduction (43 ± 13 %, P = 0.001) and tLVp (44 ± 13 %, P = 0.001), while there was no difference between intrinsic conduction and tLVp (P = 0.28). GLS was higher during BiV (14 ± 3) than during intrinsic conduction (13 ± 3, P = 0.01) and tLVp (13 ± 3, P = 0.03). Difference in time-to-peak contraction between the basal septal and lateral walls was shorter during BiV pacing (-3 ± 44 ms) than during intrinsic conduction (129 ± 66, P < 0.001) and tLVp (118 ± 118 ms, P < 0.001), with no difference between tLVp and intrinsic conduction (P = 0.56). The electrocardiogram showed change in frontal axis from intrinsic conduction in only 2 (9 %) patients during tLVp and in 20 (87 %) patients during BiV pacing. CONCLUSIONS: The acute effect of tLVp on LV systolic function and contraction pattern is significantly lower than the effect of BiV pacing and not different from intrinsic conduction in patients with LBBB and CRT.

Adding the implantable cardioverter-defibrillator to cardiac resynchronization therapy is associated with improved long-term survival in ischaemic, but not in non-ischaemic cardiomyopathy.

AIMS: Cardiac resynchronization therapy (CRT) improves symptoms, left ventricular function, and survival in patients with heart failure (HF) and wide QRS. The benefit of adding implantable cardioverter-defibrillator (ICD) backup is debated. We analysed the long-term outcome of patients with HF due to ischaemic cardiomyopathy (ICM) or non-ischaemic cardiomyopathy (NICM) treated with a CRT device with or without defibrillator backup. METHODS AND RESULTS: In this observational study, consecutive patients with an ejection fraction ≤35% and QRS width ≥120 ms receiving a CRT device at Aarhus University Hospital, Denmark from 2000 to 2010 were included. Baseline characteristics were retrieved from patient files and survival data were obtained from the Danish Civil Registration System. The primary outcome was all-cause mortality. The effect of ICD backup was estimated using Cox proportional hazards model, and the multivariate analyses were adjusted for a priori selected variables. We included 917 HF patients, 427 with NICM, and 490 with ICM. Median follow-up was 4.0 years. Adjusted hazard ratio (aHR) for all-cause mortality was 0.76 [95% confidence interval (95% CI), 0.60-0.97; P = 0.03] in all patients; 0.96 (95% CI, 0.60-1.51; P = 0.85) in patients with NICM, and 0.74 (95% CI, 0.56-0.97; P = 0.03) in patients with ICM. In patients with NICM, ICD backup seemed to be associated with improved survival among non-responders to CRT (P = 0.08), but not among responders (P = 0.61). CONCLUSION: Adding an ICD backup is associated with better survival in CRT recipients. This effect was evident among patients with ICM, but not in patients with NICM.

Early detection of atrial high rate episodes predicts atrial fibrillation and thromboembolic events in patients with cardiac resynchronization therapy.

BACKGROUND: In patients without any history of atrial fibrillation (AF), detection of subclinical atrial high rate episodes (AHRE) by implanted devices has been associated with an increased thromboembolic risk. The predictive value of AHREs in patients with cardiac resynchronization therapy (CRT) is uncertain. OBJECTIVE: We aimed to investigate the prognostic value of early detected AHRE in patients with CRT. METHODS: This observational study included patients who received CRT and no history of AF. Patients had standard indication for CRT treatment. They were screened for early detected AHREs longer than 6 minutes occurring before 6-month follow-up, and the longest duration of AHREs was recorded. Information on clinical AF and thromboembolic events was obtained from the Danish National Patient Registry. The Cox regression model was used to compute hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Of 394 eligible patients, 79 patients (20%) had early AHRE detected. During a median follow-up of 4.6 years, patients with early detected AHREs had an increased risk of clinical AF (HR 2.35; 95% CI 1.47-3.74; P < .001) and thromboembolic events (HR 2.30; 95% CI 1.09-4.83; P = .028). For patients with AHREs longer than 24 hours, these associations were stronger. The risk of mortality was not higher with early detected AHREs (HR 0.97; 95% CI 0.64-1.45; P = .87). Of the 27 patients with thromboembolic events, only 10 patients (37%) had AHREs detected within a 2-month period before the thromboembolic event. CONCLUSION: In patients without any history of AF, detection of early AHREs after CRT implantation is associated with a significantly increased risk of clinical AF and thromboembolic events, particularly AHRE longer than 24 hours.

The paced electrocardiogram cannot be used to identify left and right ventricular pacing sites in cardiac resynchronization therapy: validation by cardiac computed tomography.

AIMS: Paced electrocardiogram characteristics to confirm left ventricular (LV) and right ventricular (RV) pacing sites in cardiac resynchronization therapy (CRT) have not been validated with accurate knowledge of pacing lead positions. We aimed to evaluate the ability of the paced QRS morphology to differentiate between various LV and RV lead positions using cardiac computed tomography (CT) as the reference for LV and RV pacing site. METHODS AND RESULTS: Ninety-seven CRT patients were included. The QRS morphology was evaluated during forced LV-only and RV-only pacing. Pacing lead positions were assessed in a standard LV 16-segment model and a simplistic RV 6-segment model using cardiac CT. Ten patients with LV lead displacement or a LV pacing site outside the non-apical free wall were excluded from the analysis of the LV paced QRS complex. Pacing within the LV free wall was associated with a superior and a right-axis deviation (P = 0.02 and 0.04, respectively). Pacing from basal LV segments mainly produced a late (V5 or later) precordial QRS transition as compared with mid-LV pacing (P = 0.001). No significant associations were found between RV pacing site and QRS axis or precordial transition. Different QRS morphologies were observed during single-chamber pacing from identical LV or RV myocardial segments. CONCLUSION: Weak associations exist between LV and RV pacing sites and the paced QRS axis. None of the paced QRS characteristics can be used to reliably confirm specific LV and RV pacing sites in CRT patients.

Optimization of heart failure medication after cardiac resynchronization therapy and the impact on long-term survival.

AIMS: Treatment with evidence-based heart failure (HF) medication reduces morbidity and mortality, yet they remain underused and underdosed. Cardiac resynchronization therapy (CRT) improves haemodynamics, and might allow for optimization of HF medication. We analysed treatment with HF medication after CRT implantation, long-term adherence to this treatment, and its association with patient survival. METHODS AND RESULTS: This observational study included 826 consecutive patients who received a CRT device at a tertiary centre. Data were obtained from patient files and prescription data from the Danish National Prescription Registry. Doses are expressed as percentages of target doses. We used Cox proportional hazard model to compute adjusted hazard ratios (aHRs) for survival with 95% confidence intervals (CIs), adjusted for potential confounders. During the median (quartiles) follow-up of 4.4 (3.0-6.7) years, 324 patients died. Daily doses of beta-blocker (BB) (53 (27-90) vs. 43 (22-75)%; P < 0.001) and angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB) (78 (45-100) vs. 74 (44-97)%; P = 0.02) had increased after 6-month follow-up compared with pre-implantation doses. After 4 years, adherence was 95% to BB and 94% to ACEi/ARB. Treatments with low (≤50%) and high (>50%) doses were associated with prolonged survival for BB (low: aHR 0.65 (0.47-0.90); P = 0.009, and high: aHR 0.50 (0.35-0.70); P < 0.001) and for ACEi/ARB (low: aHR 0.68 (0.46-1.00); P = 0.05, and high: aHR 0.55 (0.38-0.80); P = 0.002). CONCLUSION: After CRT implantation, optimization of HF treatment is possible, and long-term adherence to HF medication remains high. Higher doses of BB and ACEi/ARB were associated with prolonged survival.