BACKGROUND: In aortic stenosis, the myocardium responds with left ventricular hypertrophy, which is characterized by increased left ventricular mass due to cellular hypertrophy and extracellular matrix expansion. Following aortic valve replacement (AVR), left ventricular hypertrophy regression occurs, but early cellular and extracellular dynamics are unknown. METHODS: Patients with severe symptomatic aortic stenosis undergoing surgical or transcatheter AVR were prospectively recruited. Pre- and early post-AVR cardiac magnetic resonance imaging assessed left ventricular remodeling, global longitudinal strain, and T1 mapping to determine extracellular volume fraction and volume of cellular and extracellular compartments. RESULTS: In all, 39 patients (aged 71.4±9.8 years, male 79%, aortic valve peak velocity 4.4±0.5 m/s) underwent cardiac magnetic resonance before and at median 7.7 weeks post-AVR. Left ventricular mass index reduced significantly by 15.4% ( P <0.001*), primarily driven by cellular compartment regression (18.7%, P <0.001*), with a smaller reduction in the extracellular compartment (7.2%, P <0.001*). This unbalanced regression led to an apparent increase in extracellular volume fraction (27.4±3.1% to 30.2±2.8%; P <0.001*). Although there was no significant change in global longitudinal strain post-AVR, an increase in extracellular volume fraction was associated with worsening of global longitudinal strain (Pearson r=0.41, P =0.01). Mode of intervention (transcatheter versus surgical) did not influence the above myocardial parameters post-AVR (all P >0.05). The asterisk in P values indicates a statistical significance of <0.05. CONCLUSIONS: Within 8 weeks of AVR for aortic stenosis, substantial left ventricular hypertrophy regression occurs involving both cellular and extracellular compartments, demonstrating the early myocardial adaptability to afterload relief. Cellular compartment regression is greater than extracellular regression, leading to an apparent increase in extracellular volume fraction. Mode of intervention did not affect degree of reverse remodeling, indicating that both are effective at resulting beneficial changes post-AVR. REGISTRATION: URL: https://www.isrctn.com ; Unique identifier: NCT04627987.

INTRODUCTION:In aortic stenosis (AS), the heart transitions from adaptive compensation to an AS cardiomyopathy and eventually leads to decompensation with heart failure. Better understanding of the underpinning pathophysiological mechanisms is required in order to inform strategies to prevent decompensation. AREAS COVERED:In this review, we therefore aim to appraise the current pathophysiological understanding of adaptive and maladaptive processes in AS, appraise potential avenues of adjunctive therapy before or after AVR and highlight areas of further research in the management of heart failure post AVR. EXPERT OPINION:Tailored strategies for the timing of intervention accounting for individual patient's response to the afterload insult are underway, and promise to guide better management in the future. Further clinical trials of adjunctive pharmacological and device therapy to either cardioprotect prior to intervention or promote reverse remodeling and recovery after intervention are needed to mitigate the risk of heart failure and excess mortality.

Aim: This study retrospectively analyses the impact of the 1(st) year of the COVID-19 pandemic on route of presentation and staging in lung cancer compared to the 2 years before and after implementation of the Leicester Optimal Lung Cancer Pathway (LOLCP) in Leicester, United Kingdom. Method: Electronic databases and hospital records were used to identify all patients diagnosed with lung cancer in 2018 (pre-LOLCP), 2019 (post-LOLCP), and March 2020-2021 (post-COVID-19 lockdown). Information regarding patient characteristics, performance status, stage, and route of diagnosis was documented and analysed. Emergency presentation was defined as diagnosis of new lung cancer being made after unscheduled attendance to urgent or emergency care facility. Results: Following implementation of the LOLCP pathway, there was a significant decrease in emergency presentations from 26.8 to 19.6% (p = 0.002) with a stage shift from 33.9% early stage disease to 40.3%. These improved outcomes were annulled during the COVID-19 pandemic, with emergency presentations increasing to 38.9% (p < 0.001) and a reduction in early-stage lung cancer diagnoses to 31.5%. There was a 61% decline in 2 week wait referrals but no significant decline in the LOLCP direct-to-CT referrals. Conclusion: We have demonstrated a significant increase in late-stage lung cancer diagnoses and emergency presentations during the first year of the COVID-19 pandemic. The causes for these changes are likely to be multifactorial. The long-term effect on lung cancer mortality remains to be seen and is an important focus of future study.

Introduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel-related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these comorbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity. Methods: The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis, and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment. Discussion: CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow preclinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets.

The objective of this review is to investigate the commonalities of microvascular (small vessel) disease in heart failure with preserved ejection fraction (HFpEF) and cerebral small vessel disease (CSVD). Furthermore, the review aims to evaluate the current magnetic resonance imaging (MRI) diagnostic techniques for both conditions. By comparing the two conditions, this review seeks to identify potential opportunities to improve the understanding of both HFpEF and CSVD.

Background Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. Methods CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. Results 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [ r s ] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high ( r s between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). Conclusion Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insights into arrhythmogenesis and potentially pave the way for more personalised risk stratification. Clinical trial registration: Title: Multimorbidity Life-Course Approach to Myocardial Health—A Cardiac Sub-Study of the MRC National Survey of Health and Development (NSHD) (MyoFit46). National Clinical Trials (NCT) number: NCT05455125. URL: https://clinicaltrials.gov/ct2/show/NCT05455125?term=MyoFit&draw=2&rank=1

Every child and young person has the right to breathe clean air, with healthy lungs. Preconception, in utero and early life exposures, affect children’s lungs, their lung growth and their longterm health. Government, societal and individual action to address this is needed, including the provision and distribution of the necessary resources, both to protect children now and to prevent future ill health, disability and premature death. Government, charities, professional bodies and other organisations must consider impacts on child health in all their policies and ensure that children, as well as their families and carers, have appropriate protection and support. To address this, the Asthma UK and British Lung Foundation Partnership Children’s Charter for Lung Health, endorsed by The British Paediatric Respiratory Society and the British Thoracic Society as well as the Association of Chartered Physiotherapists in Respiratory Care and the Association of Respiratory Nurse Specialistshere sets out 10 principles in three groups to guide policy development and action (figure 1).

Objective To identify the most common transthoracic echocardiogram (TTE) parameters in patients hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) and their association with myocardial injury and outcomes. Methods A retrospective, single-centre, observational, exploratory cohort study was performed at the height of the COVID-19 pandemic. All SARS-CoV-2 polymerase chain reaction (PCR) positive patients who underwent a TTE during their inpatient admission between 1 March 2020 and 31 October 2020 were analysed. The most frequent cardiovascular risk factor profile and echocardiographic features were investigated. Results A total of 87 patients met the eligibility criteria. A salient 41.4% (n=36) of our cohort succumbed to this devastating virus. More than half of our hospital population (58.6%) were admitted to the intensive care unit (ITU) and this was significantly associated with inpatient mortality (OR: 7.14, CI 2.53 to 20.19, p<0.001). Hypertension was the most common cardiovascular risk factor (51.7%) with no additional prominence in non-survivors (OR: 2.33, CI 0.97 to 5.61, p=0.059). Remarkably, 90.8% of our cohort demonstrated a preserved left ventricular ejection fraction, although 69.1% had elevated troponin levels. Only 1 patient (1.1%) was given a diagnostic label of myocarditis. A raised pulmonary artery systolic pressure (36.8%) andright ventricle (RV) dysfunction (26.4%) were the most common echocardiographic features. In particular, the presence of RV dysfunction was significantly related to adverse outcomes (OR: 2.97, CI 1.11 to 7.94, p<0.03). Conclusions In this cohort of extremely unwell patients hospitalised with COVID-19 pneumonitis, the presence of RV dysfunction or admission to ITU was significantly associated with inpatient case fatality ratio. Moreover, COVID-19-induced myocarditis remains extremely rare.

EDITORIAL article Front. Cardiovasc. Med., 19 July 2021Sec. Cardiovascular Imaging https://doi.org/10.3389/fcvm.2021.708889