Sanders, Gillian D

Introduction: To improve CRT outcomes, image-guided approaches targeting left ventricular (LV) lead placement at the segment of latest mechanical activation have been compared to non-image-guided approaches with mixed results. A meta-analysis was conducted to assess the association between an image-guided approach and CRT outcomes. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that compared any image-guided versus any non-image-guided approach for LV lead placement. Two independent reviewers screened titles and abstracts then reviewed full text of identified studies. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses were performed for NYHA class improvement and changes in LV end systolic volume, LV end diastolic volume, and LVEF using random effects models. Results: Of 5715 citations screened, 5 RCTs with a total of 818 patients met the inclusion criteria. Speckle tracking echocardiography (STE) was the primary imaging method in all studies, but 3 studies included CT, CMR, SPECT, and/or PET in addition to STE. The comparator arms were standard of care in 4 studies and an electrically guided approach in one. Mean age ranged from 66 to 72 years, 76% were male, and 53% had ischemic cardiomyopathy. Among 747 evaluable patients, concordant or adjacent LV lead was achieved in 348 of 386 (90%) in the image-guided arm and 291 of 361 (81%) in the control arm. At 6 months, the image-guided approach was statistically significantly associated with a NYHA class improvement, but no other statistically significant differences were found (Figure). Conclusion: An image-guided CRT approach was associated with significant Improvement in NYHA class but not in echocardiographic measures, possibly due to small sample size and high LV concordance with area of latest activation in both study arms - the latter of which merits further investigation.

Introduction: CRT outcomes with image-guided left ventricular (LV) lead placement within the LV segment of latest mechanical activation have been assessed in several randomized controlled trials (RCTs) with equivocal results, possibly due to variable achievement of concordant LV lead placement in the image-guided and comparator arms. We conducted meta-analyses to assess CRT outcomes associated with concordant LV lead placement. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that reported outcomes in those with LV lead placement at or adjacent to the site of latest mechanical activation (concordant) versus those with LV lead placement distant to the site of latest mechanical activation (discordant) as determined by any imaging method. Two independent reviewers screened titles and abstracts then reviewed full text for inclusion/exclusion. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses for death, death or HF hospitalization, and changes in LVESV and LVEF were performed using random effects models. Results: Among 5715 citations identified, 9 papers from 8 studies (including 4 RCTs) were selected that included 1004 patients with concordant LV lead placement and 380 with discordant LV lead placement. Mean patient age ranged from 66 to 68 years, 82% were male, and 64% had ischemic cardiomyopathy. Segment of latest activation was determined by speckle tracking echocardiography (STE) in 7 (88%) studies. Meta-analyses demonstrated statistically significant lower all-cause mortality or HF hospitalization and reduction in LVESV with a concordant LV lead (Figure). There were trends toward lower all-cause mortality and increased LVEF. Conclusion: A concordant LV lead, as determined primarily by STE, was associated with better CRT outcomes. Further study of feasible methods to achieve concordance in clinical practice is needed.

Introduction: CRT optimizations has the potential to improve the 30% non-response rate. Randomized trials (RCTs) comparing device and echo-guided CRT optimization have been overall small and results have been conflicting. Methods: We searched the EMBASE and MEDLINE databases from January 2008 through September 2020 for RCTs and prospective observational studies that randomized patients to either echo-guided or device-based CRT optimization. Included studies had to report on at least one of the following outcomes of interest: all-cause mortality, heart failure hospitalization (HFH), NYHA class improvement, mean EF at follow up, LVEDD, 6MWD, and QoL. A meta-analyses on the outcomes of interest was performed using random effects models. Results: We included seven RCTs representing a total of 2,730 patients. Of those, 1,113 patients were randomized to echo-guided optimization, and 1,617 were randomized to device-based optimization. The mean age of patients was 64.5 years, and they were predominantly men (60%). In the device-based optimization group, there was 93 deaths (5.7%) and 142 HFH (5.1%). In the echo-guided optimization group, there was 57 deaths (10.2%) and 112 HFH (12.4%). On random effects meta-analysis, the device-based optimization group had a lower rate of HFH compared with the echo-guided optimization group (OR 0.81, 95% CL 0.70-0.95, Figure). However, differences in the following outcomes between the two groups were not statistically significant: all-cause mortality, mean follow up EF, LVEDD, NYHA class improvement, 6MWD improvement range or QoL. Conclusions: This meta-analysis suggests that echo-guided optimization of CRT is equivalent to device-based optimization in relation to the clinical outcomes of death, EF, LVEDD, NYHA and 6MWD but suggests that device-related optimization could reduce HFH. The latter merits further investigation in relation to different device-base optimization algorithms.

Background— Clinical trials of implantable cardioverter defibrillators (ICDs) for primary prevention enrolled a limited number of women. We sought to examine clinical practice data to compare survival rates among women with heart failure with or without a primary prevention ICD. Methods and Results— We linked data from 264 US hospitals included in the Get With The Guidelines for Heart Failure registry with data from the Centers for Medicare and Medicaid Services. From these sources, we propensity score matched 430 women with heart failure who received a primary prevention ICD to 430 women who did not; we further adjusted using a Cox proportional hazards model. Median follow-up was 3.4 and 3.0 years. For comparison, we matched 859 men receiving an ICD with 859 who did not; median follow-up was 3.9 versus 2.9 years. In the matched cohorts, an ICD was associated with similarly better survival in women (hazard ratio, 0.78; 95% confidence interval, 0.66–0.92; P =0.003) and men (hazard ratio, 0.76; 95% confidence interval, 0.67–0.87 P <0.001). There was no interaction between sex and presence of an ICD with respect to survival ( P =0.79). Conclusions— Among patients with heart failure with reduced left ventricular ejection fraction, a primary prevention ICD was associated with a significant survival advantage among women and among men. These findings support guideline-directed use of primary prevention ICDs in eligible patients.

Background— Guidelines recommend that implantable cardioverter-defibrillator (ICD) candidates have an estimated longevity of ≥1 year. Longevity can be affected by chronic kidney disease (CKD). Methods and Results— Using the National Cardiovascular Data Registry ICD registry linked with the Social Security Death Master File, we assessed the rate of death after primary prevention ICD placement between January 1, 2006, and December 31, 2007, according to CKD stage. Using Cox models, we identified factors associated with death among patients with CKD. Compared with patients without CKD (n=26 056), those with CKD (n=21 226) were older, less commonly men, more often white, and more frequently had comorbid illness. Compared with patients without CKD, patients with a glomerular filtration rate 30 to 60, glomerular filtration rate <30, and end-stage renal disease on dialysis had a higher risk of death after ICD placement (hazard ratio, 2.08; 95% confidence interval, 1.99–2.18; P <0.0001; hazard ratio, 4.20; 95% confidence interval, 3.92–4.50; P <0.0001; and hazard ratio, 4.80; 95% confidence interval, 4.46–5.17; P <0.0001, respectively). Corresponding 1-year death rates were 4.4%, 9.1%, 20.2%, and 22.4%. Among patients with CKD, factors associated with increased risk of death included CKD severity, age >65 years, heart failure symptoms, diabetes mellitus, lung disease, serum sodium <140 mEq/L, atrial fibrillation or flutter, and a lower ejection fraction. Conclusions— The risk of death after primary prevention ICD placement is proportional to CKD severity. Among patients with CKD, several factors are prognostically significant and could inform clinical decision making on primary prevention ICD candidacy.