Aims: The randomized, double-blind, placebo-controlled HOPE-HF trial assessed the benefit of atrio-ventricular (AV) delay optimization delivered using His bundle pacing. It recruited patients with left ventricular ejection fraction ≤40%, PR interval ≥200 ms, and baseline QRS ≤140 ms or right bundle branch block. Overall, there was no significant increase in peak oxygen uptake (VO2max) but there was significant improvement in heart failure specific quality of life. In this pre-specified secondary analysis, we evaluated the impact of baseline PR interval, echocardiographic E-A fusion, and the magnitude of acute high-precision haemodynamic response to pacing, on outcomes. Methods and results: All 167 randomized participants underwent measurement of PR interval, acute haemodynamic response at optimized AV delay, and assessment of presence of E-A fusion. We tested the impact of these baseline parameters using a Bayesian ordinal model on VO2max, quality of life and activity measures. There was strong evidence of a beneficial interaction between the baseline acute haemodynamic response and the blinded benefit of pacing for VO2 (Pr 99.9%), Minnesota Living With Heart Failure (MLWHF) (Pr 99.8%), MLWHF physical limitation score (Pr 98.9%), EQ-5D visual analogue scale (Pr 99.6%), and exercise time (Pr 99.4%). The baseline PR interval and the presence of baseline E-A fusion did not have this reliable ability to predict the clinical benefit of pacing over placebo across multiple endpoints. Conclusions: In the HOPE-HF trial, the acute haemodynamic response to pacing reliably identified patients who obtained clinical benefit. Patients with a long PR interval (≥200 ms) and left ventricular impairment who obtained acute haemodynamic improvement with AV-optimized His bundle pacing were likely to obtain clinical benefit, consistent across multiple endpoints. Importantly, this gradation can be reliably tested for before randomization, but does require high-precision AV-optimized haemodynamic assessment to be performed.

Introduction Reduction of low-density lipoprotein C (LDL-C) slows progression of atherosclerosis and decreases risk of future cardiovascular events following acute coronary syndrome (ACS). However, notable differences exist between European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines on lipid lowering goals. For patients diagnosed with ACS, NICE 2023 guidance recommends a target LDL-C level of 2.0 mmol/l or less, or non-HDL cholesterol level of 2.6 mmol/l or less. NICE also recommend full lipid profile evaluation on admission and 2–3 months after starting or changing treatment. ESC 2019 dyslipidaemia guidelines recommend high intensity statin therapy for a 50% reduction in LDL-C or LDL-C levels of <1.4 mmol/l in very high-risk patients. Failure to reach lipid targets should warrant consideration of novel lipid lowering therapies. We sought to determine the proportion of patients with ACS who achieved LDL-C goals by 3 months and to assess adherence to lipid profile monitoring recommendations. Methods In this retrospective cohort analysis, patients with confirmed ACS from 1st June 2022 to 31st May 2023 were identified from our local Myocardial Ischaemia National Audit Project (MINAP) dataset. Lipid profile, baseline demographic and medical therapy data were collected from our Trust online laboratory reporting system, healthcare summary records and correspondence. Data was analysed using GraphPad Prism and Microsoft Excel. Results Of the 343 patients included in the study, mean age was 67.9 years, 67.7% were male and 12.2% had previously diagnosed dyslipdiaemia (table 1). 72.9% met the NICE target, and 34.6% met the ESC target. During admission for ACS 12.0% of patients had a lipid profile taken and 31.2% had a lipid profile <3 months following discharge (table 2). 2.9% of patients had a lipid profile both during admission and <3 months of discharge. 88.8% of patients were discharged on a statin, 3.8% on combination or newer lipid lowering therapies, and 7.4% on no lipid lowering therapy at all. Of the 301 patients discharged on a statin, 18.6% reported an intolerance or side effect. 64.3% reduced their statin dose or were prescribed an alternative statin, 5.4% were started on Ezetimibe. 23.2% received no alternative lipid lowering therapy agent. Conclusion This data demonstrates that NICE and ESC 3 month lipid targets are not being met in post ACS patients at our institution. Given the availability of new lipid lowering therapies, this study highlights that improvements in both serial lipid profile monitoring and prescription of novel therapies can be made to reduce risk of future cardiovascular events.

Atrial fibrillation (AF) remains a complex and challenging arrhythmia to treat, necessitating innovative therapeutic strategies. This review explores the evolving landscape of gene therapy for AF, focusing on targeted delivery methods, mechanistic insights, and future prospects. Direct myocardial injection, reversible electroporation, and gene painting techniques are discussed as effective means of delivering therapeutic genes, emphasizing their potential to modulate both structural and electrical aspects of the AF substrate. The importance of identifying precise targets for gene therapy, particularly in the context of AF-associated genetic, structural, and electrical abnormalities, is highlighted. Current studies employing animal models, such as mice and large animals, provide valuable insights into the efficacy and limitations of gene therapy approaches. The significance of imaging methods for detecting atrial fibrosis and guiding targeted gene delivery is underscored. Activation mapping techniques offer a nuanced understanding of AF-specific mechanisms, enabling tailored gene therapy interventions. Future prospects include the integration of advanced imaging, activation mapping, and percutaneous catheter-based techniques to refine transendocardial gene delivery, with potential applications in both ventricular and atrial contexts. As gene therapy for AF progresses, bridging the translational gap between preclinical models and clinical applications is imperative for the successful implementation of these promising approaches.

Introduction The 2021 ESC guidelines emphasise the importance of appropriate diagnosis and management of heart failure as it represents a condition with significant heterogeneity. Based on the NICOR heart failure audit 2021, the mortality rates are high with 40% of newly diagnosed patient are dying within a year and 50% of patients are either readmitted to hospital or dying within a year of admission to hospital. Pharmacotherapies such as beta blockers, angiotensin-converting enzyme inhibitors (ACEi) / angiotensin receptor neprilysin inhibitor (ARNI), sodium-glucose co-transporter 2 inhibitor (SGLTi) and mineralocorticoid receptor antagonists (MRA) have proven to show marked reduction in mortality and morbidity. It is the cornerstone prior to considering non-pharmacological interventions such as device therapy. The aim of our study is to assess prescribing practice in commencing appropriate medications in patients with heart failure with reduced ejection fraction (HFrEF) in a district general hospital setting. Method A retrospective analysis based on data from NICOR of patients presenting to Kings Mill Hospital with diagnosis of heart failure between December 2020 – December 2021 was performed. We looked into parameters such as co-morbidities including a diagnosis of pre-existing heart failure, echocardiography results, heart failure medications on admission and on discharge, blood tests (potassium levels and eGFR) and haemodynamic (blood pressure and heart rates) were collected and collated. Results A total of 219 patients with diagnosis of heart failure were admitted. The mean age is 80 years old with a slight predominance of female patients at 51%. It was noted that 55% of these admissions had pre-existing diagnosis of HFrEF. 51% of the patients had echocardiogram during the admission and 40.2% have HFrEF. The calculated mortality is 26.5% in this cohort. Patients with new diagnosis of HFrEF were better optimised with medications (Figure 1) compared to the ones with pre-existing diagnosis. Substandard heart failure medication optimisations are due to medication intolerance, worsening renal function / hyperkalemia and haemodynamic effects such as hypotension. Only 2% of patients were on SGLT2i and ARNI compared to ACEi/ARB due to lack of familiarity of indication for prescribing. All patients had appropriate potassium levels as well as establishment of optimal heart rate and blood pressure control prior to discharge. Conclusion This analysis highlights that patients are not fully optimized on oral heart failure therapies prior to hospital discharge. Robust measures must be taken in commencing on SGLT2i and ARNI. We need to take opportunities to optimise the medications of patients with established diagnosis. These findings will form the basis of our quality improvement project on heart failure medications optimization and more analysis will follow in future.

Background Association between the heart and the thyroid gland has been well-known for 200 years, from hyperthyroidism leading to cardiac arrhythmias and high-output heart failure to cardiovascular diseases in hypothyroidism through accelerated atherosclerosis and endothelial dysfunction. We present a case which demonstrates another conjunction between the heart and the thyroid. Case Presentation A 32-year-old female presented to the A&E department with chest pain, vomiting, and generalized unwellness. She has been well previously, without any underlying medical disease. Her EWS score was 7 with tachycardia and high fever. Blood results showed microcytic anaemia, leucocytosis and raised C-reactive protein. She was treated for sepsis which later turned out to be infective endocarditis. Blood culture was positive for Staph aureus. The subsequent echocardiogram showed a vegetation of 1.2cm x 0.8cm at the posterior mitral valve (figure 1). Interestingly, she was found to be hyperthyroid from thyroid screening prompted by tachycardia presentation. Thyroid stimulation hormone (TSH) was high <0.01 (0.5–5 μIU/mL). TSH receptor antibodies and thyroid peroxidase (TPO) antibodies were also high. Carbimazole and beta-blocker were initiated. Despite antibiotic therapy, the patient required mitral valve replacement because of the vegetation size, persistently raised inflammatory markers and incompetent mitral valve. Surgical findings include large vegetation on P2 segment of the mitral valve, with deep abscess cavity underneath. She was discharged without further complications and her thyroid status normalized 3 months later with carbimazole. Discussion Although thyrotoxicosis together with infective endocarditis is a rare presentation, any organ involvement is possible with endocarditis. There have been a few case reports of suppurative thyroiditis or thyroid abscess in infective endocarditis. In our case, there have been no symptoms such as neck pain or swelling and thyroid gland appears normal from CT scan. Presence of TSH receptor antibodies and TPO antibodies suggest autoimmune thyroiditis nature. Association between autoimmune thyroiditis and infected cardiac valves can be explained by several mechanisms. In Graves’ disease, circulating TSH receptor autoantibodies activate mucopolysaccharide-secreting endothelial cells leading to thickening and myxomatous changes with likelihood of endocarditis in transient bacteremia. Conversely, various infections are suggested to trigger autoimmune thyroid disorders due to the release of sequestered antigens from inflammation and molecular mimicry of the infective organisms. Psychological stress is also a factor known to precipitate autoimmunity. Infective endocarditis reflects both. Conclusion This case highlights the importance of thyroid investigation in the management of infective endocarditis. It also illustrates the possible association between autoimmune thyroid disease and infective endocarditis.

Background: Measurement of fractional flow reserve (FFR) has an established role in guiding percutaneous coronary intervention. We tested the hypothesis that, at the stage of diagnostic invasive coronary angiography, systematic FFR-guided assessment of coronary artery disease would be superior, in terms of resource use and quality of life, to assessment by angiography alone. Methods: We performed an open-label, randomized, controlled trial in 17 UK centers, recruiting 1100 patients undergoing invasive coronary angiography for the investigation of stable angina or non-ST-segment-elevation myocardial infarction. Patients were randomized to either angiography alone (angiography) or angiography with systematic pressure wire assessment of all epicardial vessels >2.25 mm in diameter (angiography+FFR). The coprimary outcomes assessed at 1 year were National Health Service hospital costs and quality of life. Prespecified secondary outcomes included clinical events. Results: In the angiography+FFR arm, the median number of vessels examined was 4 (interquartile range, 3-5). The median hospital costs were similar: angiography, £4136 (interquartile range, £2613-£7015); and angiography+FFR, £4510 (£2721-£7415; P=0.137). There was no difference in median quality of life using the visual analog scale of the EuroQol EQ-5D-5L: angiography, 75 (interquartile range, 60-87); and angiography+FFR, 75 (interquartile range, 60-90; P=0.88). The number of clinical events was as follows: deaths, 5 versus 8; strokes, 3 versus 4; myocardial infarctions, 23 versus 22; and unplanned revascularizations, 26 versus 33, with a composite hierarchical event rate of 8.7% (48 of 552) for angiography versus 9.5% (52 of 548) for angiography+FFR (P=0.64). Conclusions: A strategy of systematic FFR assessment compared with angiography alone did not result in a significant reduction in cost or improvement in quality of life.

Cardiac syncope and epileptic seizure are two very similar presentations and difficult to differentiate without a proper history, physical examination and investigations. In a former study, 10 out of 22 episodes of induced ventricular tachycardia or fibrillation can result in stereotypical tonic-clonic movement with varied electroencephalography changes. We present a case which was diagnosed as ventricular tachycardia from seizure-like attack. It is to emphasise the importance of including ventricular tachycardia among other differential diagnoses of seizure-like activity in a patient with cardiovascular risks.

Background : Class IC antiarrhythmic drug flecainide is commonly used in the management of atrial arrhythmias and in particular atrial fibrillation (AF). Although previously reported as a potential complication, atrial flutter (AFL) with 1:1 atrioventricular (AV) conduction is rare, with only few cases reported so far, most of which related to physical activity. In all previous reported cases, 1:1 conduction resulted in ventricular rates of >200 b.p.m. Case summary : We report the case of a 60-year-old woman, who presented to our local emergency department with palpitations related to acute onset AF. The patient developed symptomatic 1:1 AFL with a rate of 192 b.p.m., shortly after administration of intravenous flecainide, which spontaneously converted back to AF and subsequently to sinus rhythm, with further administration of amiodarone and beta-blocker. Discussion : The case raises awareness of this rare but potentially life-threatening complication to those using flecainide for pharmacological cardioversion of AF. QRS complex widening can be seen in the context of very rapid ventricular rates, posing additional diagnostic challenge, especially with rates of <200 b.p.m. Prescribing an AV nodal blocking agent, such as a beta-blocker, together with flecainide reduces significantly the risk of 1:1 conduction and should always be considered.