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Introduction: The high output cardiac state (HOCS) [cardiac index (CI) >4 L/min/m2 ], primarily driven by abnormally low systemic vascular resistance (SVR), is a relatively under-recognized condition. Although, majority of these patients meet criteria for heart failure (HF), their treatment should be aimed at the primary pathology, as the majority of guideline directed HF therapies can reduce SVR further., Objectives: To characterize patients with HOCS and provide valuable insight into the condition., Methods: Patients investigated by right heart catheterization (RHC) at the St. Boniface Hospital, Winnipeg, Canada between January 2009 and November 2021 were reviewed. Two groups of patients were included: 1) HOCS [CI >4 L/min/m 2 ], and 2) pre-HOCS [CI between 3.8-4.0 L/min/m 2 ]. Their medical records were reviewed to identify plausible etiologies, relevant investigations, and outcomes., Results: 177/2950 (6 %) patients met criteria for inclusion: 144/177 (81 %) with HOCS [mean age 51 years (range 19 - 82); 67/144 (47 %) female] and 33/177 (19 %) with pre-HOCS [mean age 55 years (range 30 - 83); 6/33 (18 %) female]. The most common plausible etiologies for the HOCS included anemia (36 %), obesity (34 %), cirrhosis (17 %), and lung disease (32 %). Trans-thoracic echocardiography and magnetic resonance imaging findings were non-specific and predominantly described preserved left ventricular ejection fraction, and pulmonary hypertension. The population experienced high rates of hospitalization, and significantly high mortality [36/144 (25 %) of HOCS at a median follow-up of 31.5 months, and 13/33 (39 %) of pre-HOCS at a median follow-up of 17 months]., Conclusions: HOCS is not an uncommon condition and is associated with high mortality. Current HF guideline should incorporate such evaluation into the diagnostic criteria., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Iron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment., Methods: We conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ 2 tests of Independence., Results: In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001)., Conclusion: The introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients., Competing Interests: Competing interests: YL and JC have received research funding from Octapharma and the Canadian Blood Services. SP has received research funding from Boehringer-Ingelheim and has participated in a clinical trial with Abbott within the past two years. SP is a member of a speakers’ bureau for Agence L.I.V., University of Toronto, and University Health Network. YL has acted as a consultant for Choosing Wisely Canada. SP is a member of a national heart failure advisory board that works with AstraZeneca, Boehringer-Ingelheim, Novartis, and Servier., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Our preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib., Patients and Methods: This multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR)., Results: Fifty-one patients received ramucirumab and olaparib. The RP2D was olaparib 300 mg twice daily with ramucirumab 8 mg/kg. In evaluable patients at the RP2D the ORR was 6/43 (14%) (95% CI 4.7-25.6). The median progression-free survival (PFS) was 2.8 months (95% CI 2.3-4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7-13.0). Non-statistically significant improvements in PFS and OS were observed for patients with tumours with mutations in HRD genes., Conclusions: Olaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a heavily pre-treated patient population., (© 2023. The Author(s).)