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Transthyretin (TTR) is a tetrameric protein synthesized primarily by the liver. TTR can misfold into pathogenic ATTR amyloid fibrils that deposit in the nerves and heart, causing a progressive and debilitating polyneuropathy (PN) and life-threatening cardiomyopathy (CM). Therapeutic strategies, which are aimed at reducing ongoing ATTR amyloid fibrillogenesis, include stabilization of the circulating TTR tetramer or reduction of TTR synthesis. Small interfering RNA (siRNA) or antisense oligonucleotide (ASO) drugs are highly effective at disrupting the complementary mRNA and inhibiting TTR synthesis. Since their development, patisiran (siRNA), vutrisiran (siRNA) and inotersen (ASO) have all been licensed for treatment of ATTR-PN, and early data suggest these drugs may have efficacy in treating ATTR-CM. An ongoing phase 3 clinical trial will evaluate the efficacy of eplontersen (ASO) in the treatment of both ATTR-PN and ATTR-CM, and a recent phase 1 trial demonstrated the safety of novel in vivo CRISPR-Cas9 gene-editing therapy in patients with ATTR amyloidosis. Recent results from trials of gene silencer and gene-editing therapies suggest these novel therapeutic agents have the potential to substantially alter the landscape of treatment for ATTR amyloidosis. Their success has already changed the perception of ATTR amyloidosis from a universally progressive and fatal disease to one that is treatable through availability of highly specific and effective disease-modifying therapies. However, important questions remain including long-term safety of these drugs, potential for off-target gene editing, and how best to monitor the cardiac response to treatment.Kindly check and confirm the processed running title.This is correct [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TCM) is regarded as an acute and often reversible cardiac syndrome characterised by apical ballooning of the left ventricle that occurs in the absence of coronary artery obstruction and myocarditis. The underlying pathophysiology remains largely unknown, but the most widely accepted theory is catecholamine toxicity. More recently, atypical variants of TCM have been described, and are characterised by the regional wall motion abnormalities that are observed. Mid-ventricular Takotsubo cardiomyopathy (MVTCM) is characterised by hypokinesia/akinesia of the mid left ventricular wall segments with hyperdynamic basal and apical function. This report describes the first documented case of a patient who developed MVTCM after receiving a dose of intravenous adrenaline. This case provides further evidence to support the notion that catecholamine toxicity is implicated in the pathogenesis of TCM. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review will explore the role of cardiac imaging in guiding treatment in the two most commonly encountered subtypes of cardiac amyloidosis (immunoglobulin light-chain amyloidosis [AL] and transthyretin amyloidosis [ATTR]). Recent Findings: Advances in multi-parametric cardiac imaging involving a combination of bone scintigraphy, echocardiography and cardiac magnetic resonance imaging have resulted in earlier diagnosis and initiation of treatment, while the evolution of techniques such as longitudinal strain and extracellular volume quantification allow clinicians to track individuals' response to treatment. Imaging developments have led to a deeper understanding of the disease process and treatment mechanisms, which in combination result in improved patient outcomes. Summary: The rapidly expanding treatment regimens for cardiac amyloidosis have led to an even greater reliance on cardiac imaging to help establish an accurate diagnosis, monitor treatment response and aid the adjustment of treatment strategies accordingly. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate the incidence of permanent pacemaker (PPM) implantation after cardiac surgery in our institution and investigate risk factors for PPM dependency to provide patients with accurate incidence figures at the time of consent for surgery. Methods: Data was collected retrospectively from a single tertiary institution from October 2018 to April 2019 inclusive of 403 patients. Incidence of PPM implantation after various cardiac operations was evaluated. A univariate analysis was carried out to identify the independent risk factors related to PPM implantation. Results: Ten patients required a PPM (2.48%). The most common indication for PPM implantation post-cardiac surgery was complete heart block (N = 7, 70%) followed by bradycardia/pauses (N = 2, 20%) and sick sinus syndrome (N = 1, 10%). PPM implantation after coronary artery bypass graft (CABG) surgery was the lowest (0.63%), while combined CABG and valve operations had the highest incidence (5.97%). Independent risk predictors for PPM implantation included female gender (p = 0.03), rheumatic heart disease (p = 0.008), pulmonary hypertension (p = 0.01), redo operations (p = 0.002), mitral valve procedures (p = 0.001), tricuspid valve procedures (p = 0.0003) and combined mitral and tricuspid valve procedures (p = 0.0001). Average length of intensive care unit (ICU)/high-dependency unit (HDU) stay was significantly prolonged for patients who required a PPM post-cardiac surgery. Conclusion: As clinicians, it can be challenging to provide our patients with accurate information on the risk of PPM implantation relative to their operation. A unit-specific data may be a more accurate method of informing our patients on this risk. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase inhibitors such as donepezil delay the progression of Alzheimer's dementia by increasing acetylcholine concentrations in the central nervous system. However, it is becoming apparent that cholinesterase inhibition by donepezil is not confined to the brain. This is supported by previous case reports of peripheral cholinergic side effects and adverse cardiac arrhythmias such as Torsades de Pointes which are reversible upon cessation of donepezil. The augmented acetylcholine concentrations and IKr inhibition in cardiomyocytes caused by donepezil are believed to mediate this effect. [ABSTRACT FROM AUTHOR]

Almost a third of patients fulfilling current guidelines criteria have suboptimal responses following cardiac resynchronization therapy (CRT). Circulating biomarkers may help identify these patients. We aimed to assess the predictive role of full blood count (FBC) parameters in prognosis of heart failure (HF) patients undergoing CRT device implantation. We enrolled 612 consecutive CRT patients and FBC was measured within 24 hours prior to implantation. The follow-up period was a median of 1652 days (IQR: 837–2612). The study endpoints were i) composite of all-cause mortality or transplant, and ii) reverse left ventricular (LV) remodeling. On multivariate analysis [hazard ratio (HR), 95% confidence interval (CI)] only red cell count (RCC) (p = 0.004), red cell distribution width (RDW) (p < 0.001), percentage of lymphocytes (p = 0.03) and platelet count (p < 0.001) predicted all-cause mortality. Interestingly, RDW (p = 0.004) and platelet count (p = 0.008) were independent predictors of reverse LV remodeling. This is the first powered single-centre study to demonstrate that RDW and platelet count are independent predictors of long-term all-cause mortality and/or heart transplant in CRT patients. Further studies, on the role of these parameters in enhancing patient selection for CRT implantation should be conducted to confirm our findings. [ABSTRACT FROM AUTHOR]