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Aim: To evaluate use of CIED-generated Heart Failure Risk Score (HFRS) alerts in an integrated, multi-disciplinary approach to HF management. Methods: We undertook a prospective, single centre outcome study of patients implanted with an HFRS-enabled Medtronic CIED, generating a “high risk” alert between November 2018 and November 2020. All patients generating a “high risk” HFRS alert were managed within an integrated HF pathway. Alerts were shared with local HF teams, prompting patient contact and appropriate intervention. Outcome data on health care utilisation (HCU) and mortality were collected. A validated questionnaire was completed by the HF teams to obtain feedback. Results: 367 “High risk” alerts were noted in 188 patients. The mean patient age was 70 and 49% had a Charlson Comorbidity Score of >6. Mean number of alerts per patients was 1.95 and 44 (23%) of patients had >3 “high risk” alerts in the follow up period. Overall, 75 (39%) patients were hospitalised in the 4–6-week period of the alert; 53 (28%) were unplanned of which 24 (13%) were for decompensated HF. A total of 33 (18%) patients died in the study period. Having three or more alerts significantly increased the risk of hospitalisation for heart failure (HR 2.5, CI 1.1–5.6 p = 0.03). The feedback on the pathway was positive. Conclusions: Patients with “high risk” alerts are co-morbid and have significant HCU. An integrated approach can facilitate timely risk stratification and intervention. Intervention in these patients is not limited to HF alone and provides the opportunity for holistic management of this complex cohort.

Aims/Background Heart failure affects approximately 1 million people in the UK, adversely affecting quality of life, functional capacity and cognitive health. Iron deficiency complicates heart failure in approximately 50% of patients. Giving intravenous ferric carboxymaltose has been shown to improve quality of life in patients with heart failure (New York Heart Association class and Kansas City Cardiomyopathy Questionnaire). Methods A quality improvement project was designed to assess the feasibility, safety and cost implications of establishing an intravenous iron service in the authors' centre. Results Between July and December 2019 61 patients who were screened met the inclusion criteria and were administered intravenous ferric carboxymaltose. There were statistically significant improvements in ferritin levels (83.3 ug/litre to 433 ug/litre; P<0.0001), transferrin saturation (18% to 30% P<0.0001) and haemoglobin levels (126 g/litre to 135 g/litre; P<0.01). No demonstrable changes in New York Heart Association class or quality of life scores were noted. The overall financial impact for the trust was income generation of £14 665, a net income of £240 per patient. Conclusions Intravenous iron replacement with ferric carboxymaltose is safe and cost effective, and should be considered in eligible iron-deficient patients with symptomatic heart failure. Integration with another day case intravenous service represented the most logistically simple and economically viable method of service delivery.

Lapatinib is an EGFR/HER2 tyrosine kinase inhibitor (TKI) that has been approved for clinical use in HER2 positive breast cancer patients who have progressed on previous Trastuzumab containing regimens. However, lapatinib monotherapy only delays tumour growth in HER2 positive xenograft models and has only modest clinical activity in breast cancer patients. There is a further need to understand its mechanisms of action and resistance. We aimed to assess the acute effect of lapatinib on HER2 phosphorylation in HER2 positive breast cancer cells since previous work from our lab showed that inadequate suppression of HER2 phosphorylation by gefitinib and trastuzumab may lead to acquired drug resistance. Traditionally, the phosphorylation status of HER proteins is determined by phosphor-tyrosine western blotting followed by immunoprecipitation. The limitation of this technique includes false positive due to signals from co-precipitated proteins of the same size as target, which is even more prominent with the HER family of protein. With the use of phosphorylated protein-specific antibody, we found that, contrary to general belief, lapatinib could not abolish HER2 phosphorylation in HER2 over-expressed breast cancer cell lines under serum-supplemented condition. It was thought that the growth factors in the serum activate other HER receptors to maintain HER2 phosphorylation. Indeed, Lapatinib could reduce phospho-HER2 level in serum-starved breast cancer cell lines; however, it failed to reverse heregulin-induced HER signalling activation and downstream MAPK and AKT signalling. The combination of lapatinib and pertuzumab drastically inhibited ligand-induced HER family phosphorylation and downstream signalling. HER3 was reported as an important biomarker for resistance in HER family targeted therapy. This novel combination could inhibit HER3 phosphorylation and its downstream AKT pathway more than lapatinib or pertuzumab alone; this finding also correlated with cancer cell viability, as the combination of lapatinib and pertuzumab reduced cell viability more than either drug alone. These results might indicate a new strategy of drug combination to tackle resistance in HER2 targeted therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1226. doi:1538-7445.AM2012-1226

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Liverpool Clinical Commissioning Group Background Heart failure (HF) is associated with significant morbidity and mortality. (1) Cardiac Implantable Electronic Devices (CIED) generated Heart Failure Risk Score (HFRS) alerts may guide management in this complex cohort and help direct resources to appropriate patients. (2) Aim  To develop and evaluate an integrated, multidisciplinary approach to HF management for patients with CIED by sharing HFRS alerts directly with the HF teams. Methods We undertook a prospective, single centre cohort study of patients who generated high risk HFRS alerts. These alerts were shared with community HF teams responsible for routine care of patient, prompting patient contact and appropriate intervention by the team. Impact of the pathway was evaluated by review of outcomes including hospitalisation and clinical intervention within 4- 6 weeks of the alert and mortality during the follow up period. Ongoing education was provided to help teams deal with alerts. A validated user questionnaire was completed by the stake holders to obtain user feedback. Results 365 "High risk" alerts were noted in 188 patients in a 2 year period (November 2018 - November 2020). The mean number of alerts per patients was 1.9 and 44 (23%) of patients had &gt;3 "high risk" alerts in the follow up period. Having three or more alerts significantly increased the risk of hospitalisation for heart failure (HR 2.5, CI 1.1–5.6 p = 0.03) but not mortality (HR 2.1 CI 0.6-7.2 p = 0.23). Overall 75 (39%) of patients were hospitalised in the 4-6 week period of the alert – 53 (28%) of these were unplanned of which 24(13%) were for decompensated HF. A further 24(13%) had planned admissions for care to improve therapy (AV node ablation, device and lead replacement) and reduce morbidity (LA appendage occlude, IV Iron therapy). 33(18%) of patients died in the follow up period.  15(8%) received therapy from the device. 18(10%) of patient underwent deactivation of ICD therapy. Contact was established in 176 (94%) of patients, and alerts actioned appropriately. 55 patients reported being asymptomatic, and in 45 the trends were improving so no further clinical action was taken. 76 patients had an onward referral made for further management including; 32 to a Cardiologist, 20 to primary care, 13 referrals to community HF teams and 11 referrals to palliative care. 23 patients had medications changes instituted. The feedback on the pathway was positive.  Conclusions  An integrated approach to HF for patients with CIEDs in situ can facilitate timely risk stratification and intervention in this cohort of patients and potentially reduce unplanned health care utilisation. Intervention in these patients is not limited to HF alone and provides the opportunity for holistic management of this complex cohort Abstract Figure.