Comparison of the Effect of Sacubitril/Valsartan on Left Ventricular Systolic Function in Patients with Non-ischaemic and Ischaemic Cardiomyopathy.

PURPOSE: Sacubitril/valsartan has been demonstrated to improve prognosis and outcomes in heart failure with reduced ejection fraction (HFrEF) patients. We sought to compare the improvement in cardiac function between non-ischaemic and ischaemic cardiomyopathy for patients receiving sacubitril/valsartan. METHODS: We conducted a single centre prospective cohort survey of patients reviewed in the Heart Function Clinic between February 2017 and January 2018. Functional evaluation and measurement of biochemical and echocardiographic parameters occurred before the initiation of sacubitril/valsartan, and after 3 months of treatment. RESULTS: We identified 52 patients (26 non-ischaemic and 26 ischaemic cardiomyopathy) suitable for treatment with sacubitril/valsartan. Treatment was followed by a significant decrease in a New York Heart Association (NYHA) class in both patients with non-ischaemic (2.3 ± 0.6 vs. 1.6 ± 0.7, P < 0.001) and ischaemic cardiomyopathy (2.3 ± 0.5 vs. 1.5 ± 0.6, P < 0.001), along with an increase in ejection fraction in both patients with non-ischaemic (26.2% ± 6.5% vs. 37.2% ± 13.8%, P < 0.001) and ischaemic cardiomyopathy (28.1% ± 5.7% vs. 31.5% ± 8.4%, P = 0.007). The improvement in ejection fraction was significantly greater in the patients with non-ischaemic cardiomyopathy compared to those with ischaemic cardiomyopathy (10.7% ± 13.0% vs. 3.9% ± 6.0%, P = 0.023). CONCLUSION: Our study suggests that treatment with sacubitril/valsartan in patients with non-ischaemic cardiomyopathy is followed by a greater improvement in ejection fraction than in patients with ischaemic cardiomyopathy.

Audit of the prevalence and investigation of iron deficiency anaemia in patients with heart failure in hospital practice.

PURPOSE OF THE STUDY: Iron deficiency anaemia (IDA) is associated with increased morbidity and mortality in heart failure patients. The aim of our audit was to evaluate the current practice in diagnosis and assessment of IDA in patients admitted with heart failure. STUDY DESIGN: We conducted a retrospective audit of patients admitted to our hospital between January 2017 and June 2017 with a diagnosis of heart failure, and obtained data regarding each patient's demographics and anaemic status. We also conducted a qualitative survey to assess healthcare professionals' ability to diagnose IDA, and their knowledge of iron replacement in heart failure patients. RESULTS: Our audit identified 218 heart failure patients, nearly two-thirds (n=138, 63.3%) of which were anaemic. Of the 138 anaemic patients, only 40 had a full haematinic screen compared with 98 who had incomplete investigations (29% vs 71%, p=0.007). Iron studies were the most commonly performed haematinic investigation (n=87, 63%), and over half of these patients were iron deficient (n=49, 56.3%). Only 12 (24.5%) iron deficient patients were prescribed oral iron therapy, while 37 (75.5%) were left without iron replacement (X2=12.8, p=0.0003). Our survey demonstrated a lack of awareness among healthcare professionals with only 19.7% of participants being able to correctly define anaemia and 9.1% being aware of guidelines regarding treatment of IDA. CONCLUSION: Many patients admitted to hospital with heart failure also have a concomitant diagnosis of anaemia. The aetiology of the underlying anaemia is often poorly investigated, and where IDA is identified it is poorly treated.

EB1 regulates attachment of Ska1 with microtubules by forming extended structures on the microtubule lattice.

Kinetochore couples chromosome movement to dynamic microtubules, a process that is fundamental to mitosis in all eukaryotes but poorly understood. In vertebrates, spindle-kinetochore-associated (Ska1-3) protein complex plays an important role in this process. However, the proteins that stabilize Ska-mediated kinetochore-microtubule attachment remain unknown. Here we show that microtubule plus-end tracking protein EB1 facilitates Ska localization on microtubules in vertebrate cells. EB1 depletion results in a significant reduction of Ska1 recruitment onto microtubules and defects in mitotic chromosome alignment, which is also reflected in computational modelling. Biochemical experiments reveal that EB1 interacts with Ska1, facilitates Ska1-microtubule attachment and together stabilizes microtubules. Structural studies reveal that EB1 either with Ska1 or Ska complex forms extended structures on microtubule lattice. Results indicate that EB1 promotes Ska association with K-fibres and facilitates kinetochore-microtubule attachment. They also implicate that in vertebrates, chromosome coupling to dynamic microtubules could be mediated through EB1-Ska extended structures.