A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A proof of concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site; (2) the LMC viable segments adjacent to the LEA site; (3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (P = .002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, P = .003; odds ratio 7.33, 95% confidence interval 1.53-35.14, P = .013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSION: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation­induced apoptosis via the Akt/GSK3ß and Bcl­2 signaling pathways.

The poor survival rate of transplanted mesenchymal stem cells (MSCs) within the ischemic heart limits their therapeutic potential for cardiac repair. Adrenomedullin (ADM) has been identified as a potent apoptotic inhibitor. The present study aimed to investigate the protective effects of ADM on MSCs against hypoxia and serum deprivation (H/SD)­induced apoptosis, and to determine the potential underlying mechanisms. In the present study, a recombinant adenovirus expressing the ADM gene was established and was infected into MSCs. The infection rate was determined via microscopic detection of green fluorescence and flow cytometric analysis. The mRNA expression levels of ADM were detected by reverse transcription­polymerase chain reaction. In addition, a model of H/SD was generated. The MSCs were randomly separated into six groups: Control, enhanced green fluorescent protein (EGFP)­Adv, EGFP­ADM, H/SD, EGFP­Adv + H/SD and EGFP­ADM + H/SD. Cell viability and proliferation were determined using the Cell Counting kit­8 assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase­mediated­dUTP nick­end labeling assay and flow cytometric analysis using Annexin V­phycoerythrin/7­aminoactinomycin D staining. The protein expression levels of total protein kinase B (Akt), phosphorylated (p)­Akt, total glycogen synthase kinase (GSK)3ß, p­GSK3ß, B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein (Bax), caspase­3 and cleaved caspase­3 were detected by western blot analysis. The results indicated that ADM overexpression could improve MSC proliferation and viability, and protect MSCs against H/SD­induced apoptosis. In addition, ADM overexpression increased Akt and GSK3ß phosphorylation, and Bcl­2/Bax ratio, and decreased the activation of caspase­3. These results suggested that ADM protects MSCs against H/SD­induced apoptosis, which may be mediated via the Akt/GSK3ß and Bcl­2 signaling pathways.