Structure determination and analysis of titin A-band fibronectin type III domains provides insights for disease-linked variants and protein oligomerisation.

Titin is the largest protein found in nature and spans half a sarcomere in vertebrate striated muscle. The protein has multiple functions, including in the organisation of the thick filament and acting as a molecular spring during the muscle contraction cycle. Missense variants in titin have been linked to both cardiac and skeletal myopathies.

Left ventricular anatomy in obstructive hypertrophic cardiomyopathy: beyond basal septal hypertrophy.

Aims: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic obstruction of the left ventricular (LV) outflow tract (LVOT). Although this may be mediated by interplay between the hypertrophied septal wall, systolic anterior motion of the mitral valve, and papillary muscle abnormalities, the mechanistic role of LV shape is still not fully understood. This study sought to identify the LV end-diastolic morphology underpinning oHCM.

Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT).

Objective: Many patients presenting with suspected acute coronary syndrome (ACS) have high-sensitivity cardiac troponin (hs-cTn) concentrations between rule-in and rule-out thresholds and hence need serial testing, which is time consuming. The Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT) assessed the utility of coronary CT angiography (CCTA) in patients with suspected ACS, non-ischaemic ECG and intermediate initial hs-cTn concentration.

Methods: Patients were randomised to CCTA-guided management versus standard of care (SOC).

Association of Titin Variations With Late-Onset Dilated Cardiomyopathy.

Importance: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM).

Objective: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM.

Healthcare resource use associated with the diagnosis of transthyretin amyloidosis cardiomyopathy.

Objectives: Our primary aim was to evaluate the healthcare resource use associated with the diagnosis of transthyretin amyloidosis cardiomyopathy. Second, we aim to assess the effect of the number of diagnostic tests and clinical contact points on the total time and costs between symptom onset and diagnosis defining a quantitative hypothetical optimized diagnostic pathway.

Setting: Clinical and cost data were collected from patients presenting between 2010 and 2018 in a tertiary referral institution in South London involving two participating hospitals.

The Role of AI in Characterizing the DCM Phenotype.

Dilated Cardiomyopathy is conventionally defined by left ventricular dilatation and dysfunction in the absence of coronary disease. Emerging evidence suggests many patients remain vulnerable to major adverse outcomes despite clear therapeutic success of modern evidence-based heart failure therapy. In this era of personalized medical care, the conventional assessment of left ventricular ejection fraction falls short in fully predicting evolution and risk of outcomes in this heterogenous group of heart muscle disease, as such, a more refined means of phenotyping this disease appears essential.

Epidemiology of cardiomyopathies and incident heart failure in a population-based cohort study.

Aims: The population prevalence of cardiomyopathies and the natural history of symptomatic heart failure (HF) and arrhythmia across cardiomyopathy phenotypes is poorly understood. Study aims were to estimate the population-diagnosed prevalence of cardiomyopathies and describe the temporal relationship between a diagnosis of cardiomyopathy with HF and arrhythmia.

Methods: People with cardiomyopathy (n=4116) were identified from linked electronic health records (~9 million individuals; 2000-2018) and categorised into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM) and cardiac amyloidosis (CA).

Real-world evidence in a national health service: results of the UK CardioMEMS HF System Post-Market Study.

Aims: The CardioMEMS HF System Post-Market Study (COAST) was designed to evaluate the safety, effectiveness, and feasibility of haemodynamic-guided heart failure (HF) management using a small sensor implanted in the pulmonary artery of New York Heart Association (NYHA) Class III HF patients in the UK, Europe, and Australia.

Methods And Results: COAST is a prospective, international, multicentre, open-label clinical study (NCT02954341). The primary clinical endpoint compares annualized HF hospitalization rates after 1 year of haemodynamic-guided management vs.

A case of mistaken arrhythmogenic identity during pregnancy.

Atypical LVOT ectopy can present with an RVOT morphology on ECG and differentiation to reveal this focus is in favor of benign idiopathic ventricular ectopy over an arrhythmogenic cardiomyopathy.

The alcohol-induced cardiomyopathy: A cardiovascular magnetic resonance characterization.

Background: Alcoholic cardiomyopathy(ACM) is part of the non-ischaemic dilated cardiomyopathy(NI-DCM) spectrum. Little is known about cardiovascular magnetic resonance(CMR) features in ACM patients. The aim of this study is to describe CMR findings and their prognostic impact in ACM patients.

ESC EORP Cardiomyopathy Registry: real-life practice of genetic counselling and testing in adult cardiomyopathy patients.

Aims: Cardiomyopathies comprise a heterogeneous group of diseases, often of genetic origin. We assessed the current practice of genetic counselling and testing in the prospective European Society of Cardiology EURObservational Research Programme Cardiomyopathy Registry.

Methods And Results: A total of 3208 adult patients from 69 centres in 18 countries were enrolled.

Differentiation between athlete's heart and dilated cardiomyopathy in athletic individuals.

Objective: Distinguishing early dilated cardiomyopathy (DCM) from physiological left ventricular (LV) dilatation with LV ejection fraction <55% in athletes (grey zone) is challenging. We evaluated the role of a cascade of investigations to differentiate these two entities.

Methods: Thirty-five asymptomatic active males with DCM, 25 male athletes in the 'grey zone' and 24 male athletes with normal LV ejection fraction underwent N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, ECG and exercise echocardiography.

High-sensitive troponin is associated with subclinical imaging biosignature of inflammatory cardiovascular involvement in systemic lupus erythematosus.

Background: Cardiovascular (CV) involvement in patients with systemic lupus erythematosus (SLE) is presumably subclinical for the major part of its evolution. We evaluated the associations between high-sensitive troponin T (hs-TropT), a sensitive marker of myocardial injury, and CV involvement using cardiac magnetic resonance (CMR).

Methods And Results: This is a two-centre (London and Frankfurt) CMR imaging study at 3.

Native T1 and ECV of Noninfarcted Myocardium and Outcome in Patients With Coronary Artery Disease.

Background: Coronary artery disease (CAD) remains the major cause of cardiac morbidity and mortality worldwide, despite the advances in treatment with coronary revascularization and modern antiremodeling therapy. Risk stratification in CAD patients is primarily based on left ventricular volumes, ejection fraction (LVEF), risk scores, and the presence and extent of late gadolinium enhancement (LGE). The prognostic role of T1 mapping in noninfarcted myocardium in CAD patients has not yet been determined.

Comprehensive use of cardiac computed tomography to guide left ventricular lead placement in cardiac resynchronization therapy.

Background: Optimal lead positioning is an important determinant of cardiac resynchronization therapy (CRT) response.

Objective: The purpose of this study was to evaluate cardiac computed tomography (CT) selection of the optimal epicardial vein for left ventricular (LV) lead placement by targeting regions of late mechanical activation and avoiding myocardial scar.

Methods: Eighteen patients undergoing CRT upgrade with existing pacing systems underwent preimplant electrocardiogram-gated cardiac CT to assess wall thickness, hypoperfusion, late mechanical activation, and regions of myocardial scar by the derivation of the stretch quantifier for endocardial engraved zones (SQUEEZ) algorithm.

Native T1 and T2 mapping by CMR in lupus myocarditis: Disease recognition and response to treatment.

Background: Lupus myocarditis is likely more common than recognized clinically due to non-specific symptoms and lack of reliable non-invasive diagnostic tests. We investigated the role of native T1 and T2 in recognition of active myocardial inflammatory involvement in patients with systemic lupus erythematous (SLE).

Methods: 76 patients with clinically suspected lupus myocarditis (14 males, age: 44±16years) underwent quantitative tissue characterization with native T1 and T2 mapping.

T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure.

Objectives: The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome.

Background: NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely.

Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing.

Aims: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility of targeted exome screening in SADS victims, utilizing familial clinical screening whenever possible.

Focal But Not Diffuse Myocardial Fibrosis Burden Quantification Using Cardiac Magnetic Resonance Imaging Predicts Left Ventricular Reverse Modeling Following Cardiac Resynchronization Therapy.

Introduction: Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis.

Feasibility of high-resolution quantitative perfusion analysis in patients with heart failure.

Background: Cardiac magnetic resonance (CMR) is playing an expanding role in the assessment of patients with heart failure (HF). The assessment of myocardial perfusion status in HF can be challenging due to left ventricular (LV) remodelling and wall thinning, coexistent scar and respiratory artefacts. The aim of this study was to assess the feasibility of quantitative CMR myocardial perfusion analysis in patients with HF.

Three-dimensional atrial wall thickness maps to inform catheter ablation procedures for atrial fibrillation.

Aims: Transmural lesion formation is critical to success in atrial fibrillation ablation and is dependent on left atrial wall thickness (LAWT). Pre- and peri-procedural planning may benefit from LAWT measurements.

Methods And Results: To calculate the LAWT, the Laplace equation was solved over a finite element mesh of the left atrium derived from the segmented computed tomographic angiography (CTA) dataset.