Citations

To date, biventricular pacing (BiVP) has been the standard pacing modality for cardiac resynchronisation therapy. However, it is non-physiological, with the activation spreading between the left ventricular epicardium and right ventricular endocardium. Up to one-third of patients with heart failure who are eligible for cardiac resynchronisation therapy do not derive benefit from BiVP. Conduction system pacing (CSP), which includes His bundle pacing and left bundle branch area pacing, has emerged as an alternative to BiVP for cardiac resynchronisation. There is mounting evidence supporting the benefits of CSP in achieving synchronous ventricular activation and repolarisation. The aim of this review is to summarise the current options and outcomes of CSP when used for cardiac resynchronisation in patients with heart failure.

Abstract Cancer Associated Macrophage Like cells (CAMLs) are antigen presenting circulating stromal cells found in the blood of cancer patients (pts). Recently, PD-L1 expression on CAMLs was described in breast (BC), lung (LC) and renal cell carcinomas (RCC), appearing to parallel the inflammatory PD-L1 state of the tumor microenvironment, and acting as a possible predictive biomarker for PD-L1/PD-1 immunotherapeutics (IMTs). We monitored CAML PD-L1 from 48 pts in an array of solid tumors, prior PD-L1/PD-1 IMTs induction, to evaluate CAML’s ability to predict response by progression free survival (PFS) and overall survival (OS). Three single blind multi-year prospective studies were run to test PD-L1 CAML expression against PFS & OS, prior to induction of therapy in metastatic (m) LC (n=24), mBC (n=16) or mRCC (n=8). We recruited pts with pathologically confirmed progressing disease after at least one failed prior line of therapy. Blood samples (7.5 mL) were taken prior to start of new therapeutic regimes, i.e. pembrolizumab (n=36) or nivolumab (n=12). Whole blood was filtered by CellSieve microfilters to collect CAMLs, stain for PD-L1, and then scored as a binary high or low, to evaluate PFS & OS hazard ratios (HRs) by censored univariate & multivariate analysis at 24 months. CAMLs were found in 98% of all tested samples. Overall, pts with high CAML PD-L1 expression treated with IMT had significantly better PFS (HR=2.9, 95%CI=1.4–6.1, p=0.0067) and better OS (HR=2.7, 95%CI=1.2–6.1, p=0.0317) vs patients with low CAML PD-L1. These data suggests that PD-L1 expression in circulating CAMLs appears to predict pts with increased benefit to PD-L1/PD-1 IMTs in an array of tumor subtypes, though larger studies are needed to validate these findings. Private Funding by Creatv MicroTech, Inc. and supported grants by NCI-NIH (R43CA206840), and the Defense Advanced Research Projects Agency (DARPA)(W911NF-14-C-0098).

AbstractIntroductionLeft bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta‐analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT.MethodsWe searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel–Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity.ResultsTen studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49–14.87, I2 = 95%, p < .01, minutes) as well as a shorter procedural time (MD 33.68, 95% CI: 17.80–49.55, I2 = 73%, p < .01, minutes) during the implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRS duration (MD 25.13, 95% CI: 20.06–30.20, I2 = 51%, p < .01, milliseconds), a greater left ventricular ejection fraction improvement (MD: 5.80, 95% CI: 4.81–6.78, I2 = 0%, p < .01, percentage), and a greater left ventricular end‐diastolic diameter reduction (MD: 2.11, 95% CI: 0.12–4.10, I2 = 18%, p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05–0.68, I2 = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all‐cause mortality (RR: 0.48, 95% CI: 0.25–0.90, I2 = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19–0.82, I2 = 0%, p = .01). However, all‐cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21–4.68, I2 = 0%, p = .87).ConclusionThis meta‐analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta‐analysis alone, given the limitations stated. Dedicated, well‐designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long‐term efficacy and safety of LBBP CRT versus BIV CRT.

Background: Long-term outcomes of lead management strategies of lead abandonment (LA) or transvenous lead extraction (TLE) during cardiac implantable electronic devices (CIED) procedures requiring lead addition or replacement remain unclear. Hypothesis: We hypothesized that there is no difference in long-term (10-year) outcomes of LA versus TLE during CIED procedures requiring lead addition. Methods: We performed a retrospective cohort study of a population residing in seven adjacent counties of southeastern Minnesota with follow-up at the Mayo Clinic and its health systems. Patients who underwent LA or TLE for sterile leads from January 1, 2000, to January 1, 2011, and had follow-up for at least 10-years or until their death were included. Outcomes were identified through a detailed chart review of the electronic health record from within the Mayo Clinic system. Results: A total of 172 patients were included in the study with 153 patients who underwent LA and 19 who underwent TLE for sterile leads. In long-term follow-up, indications for subsequent lead extraction arose in 9.1% (n=14) of patients with initial LA and 5.3% (n=1) in patients with initial TLE, after an average of 7-years. Moreover, out of 14 patients, who required secondary extraction in the LA cohort, 28.6% did not proceed with the extraction. Of the remaining 10 patients, 60% had clinical success and 40% had a clinical failure with the extraction. Subsequent device upgrades or revisions were performed in 18.3% of patients in the LA group and 31.6% in the TLE group, with no significant differences in procedural challenges such as requiring balloon venoplasty or serial dilation (5.2% vs. 5.3%, P=1.0). There was no difference in 10-year survival probability among LA group and TLE group (P=0.64). Conclusion: Indications for subsequent extraction arose in 9.1% of patients with the initial LA approach for sterile leads after an average of 7.3 years and 28.6% did not proceed with the extraction. Of the patients who underwent the subsequent extraction, 60% had clinical success and 40% had a clinical failure. There was no difference in 10-year survival probability between patients with the initial LA approach or TLE approach.