Empagliflozin to prevent progressive adverse remodelling after myocardial infarction (EMPRESS-MI): rationale and design.

AIMS: Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are at risk of progressive adverse cardiac remodelling that can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients. METHODS AND RESULTS: EMpagliflozin to PREvent worSening of left ventricular volumes and Systolic function after Myocardial Infarction (EMPRESS-MI) is a randomized, double-blind, placebo-controlled, multi-centre trial designed to assess the effect of empagliflozin on cardiac remodelling evaluated using cardiovascular magnetic resonance (CMR) in 100 patients with left ventricular systolic dysfunction following MI. Eligible patients were those ≥12 h and ≤14 days following acute MI, with an LVEF <45% by CMR. Patients were randomized to empagliflozin 10 mg once a day or matching placebo. The primary outcome will be change in left ventricular end-systolic volume indexed to body surface area over 24 weeks from randomization. Secondary endpoints include measures of left ventricular and atrial volumes, left ventricular mass, LVEF, and circulating cardiac biomarkers. CONCLUSIONS: EMPRESS-MI will assess the effect of the SGLT2 inhibitor empagliflozin on cardiac remodelling in patients with left ventricular systolic dysfunction after an acute MI.

Arteriovenous fistula for haemodialysis as a predictor of de novo heart failure in kidney transplant recipients.

Background: The haemodynamic effects of a functioning haemodialysis arteriovenous fistula (AVF) can cause or exacerbate heart failure (HF). We investigated whether the presence of an AVF at the time of kidney transplant (KT) is associated with de novo HF. Methods: This was an observational cohort study including adult patients who received a KT in the West of Scotland between 2010 and 2020. We evaluated the risk and associations of pretransplant factors with de novo HF, alone and as a composite cardiovascular (CV) outcome (including non-fatal myocardial infarction, non-fatal stroke, de novo HF and CV death). Multivariable proportional hazards regression and sensitivity analyses were used to identify independent correlates of the outcomes. Results: Among 1330 included patients, the incident rate of de novo HF after transplantation was 58/1000 person-years [95% confidence interval (CI) 50-67] in AVF patients (n = 716) compared with 33/1000 person-years (95% CI 27-41) in non-AVF patients (n = 614). De novo HF was associated with the presence of an AVF [adjusted hazard ratio (aHR) 2.14 (95% CI 1.40-3.26)], duration of dialysis [aHR 1.03/year increase (95% CI 1.01-1.04)], age at transplant [aHR 1.03/year increase (95% CI 1.02-1.05)], female sex [aHR 1.93 (95% CI 1.40-2.65)] and pretransplant diabetes [aHR 2.43 (95% CI 1.48-4.01)]. The presence of an AVF was also associated with the composite CV outcome [aHR 1.91 (95% CI 1.31-2.78)]. Conclusions: The presence of an AVF may be an underrecognized modifiable predictor of de novo HF posttransplantation.

Characterizing Cardiac Function in ICU Survivors of Sepsis: A Pilot Study Protocol.

Background: Sepsis is one of the most common reasons for ICU admission and a leading cause of mortality worldwide. More than one-half of survivors experience significant physical, psychological, or cognitive impairments, often termed post-intensive care syndrome (PICS). Sepsis is recognized increasingly as being associated with a risk of adverse cardiovascular events that is comparable with other major cardiovascular risk factors. It is plausible that sepsis survivors may be at risk of unidentified cardiovascular disease, and this may play a role in functional impairments seen after ICU discharge. Research Question: What is the prevalence of myocardial dysfunction after an ICU admission with sepsis and to what extent might it be associated with physical impairments in PICS? Study Design and Methods: Characterisation of Cardiovascular Function in ICU Survivors of Sepsis (CONDUCT-ICU) is a prospective, multicenter, pilot study characterizing cardiovascular function and functional impairments in survivors of sepsis taking place in the west of Scotland. Survivors of sepsis will be recruited at ICU discharge and followed up 6 to 10 weeks after hospital discharge. Biomarkers of myocardial injury or dysfunction (high sensitivity troponin and N-terminal pro B-type natriuretic peptide) and systemic inflammation (C-reactive protein, IL-1ß, IL-6, IL-10, and tumor necrosis factor alpha) will be measured in 69 patients at recruitment and at follow-up. In addition, a cardiovascular magnetic resonance substudy will be performed at follow-up in 35 patients. We will explore associations between cardiovascular magenetic resonance indexes of cardiac function, biomarkers of cardiac dysfunction and inflammation, and patient-reported outcome measures. Interpretation: CONDUCT-ICU will provide data regarding the cause and prevalence of cardiac dysfunction in survivors of sepsis and will explore associations with functional impairment. It will provide feasibility data and operational learning for larger studies investigating mechanisms of functional impairment after ICU admission and the association between sepsis and adverse cardiovascular events. Trial Registry: ClinicalTrials.gov; No.: NCT05633290; URL: www.clinicaltrials.gov.

Socioeconomic deprivation and illness trajectory in the Scottish population after COVID-19 hospitalization.

BACKGROUND: The associations between deprivation and illness trajectory after hospitalisation for coronavirus disease-19 (COVID-19) are uncertain. METHODS: A prospective, multicentre cohort study was conducted on post-COVID-19 patients, enrolled either in-hospital or shortly post-discharge. Two evaluations were carried out: an initial assessment and a follow-up at 28-60 days post-discharge. The study encompassed research blood tests, patient-reported outcome measures, and multisystem imaging (including chest computed tomography (CT) with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging). Primary and secondary outcomes were analysed in relation to socioeconomic status, using the Scottish Index of Multiple Deprivation (SIMD). The EQ-5D-5L, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire-4 (PHQ-4) for Anxiety and Depression, and the Duke Activity Status Index (DASI) were used to assess health status. RESULTS: Of the 252 enrolled patients (mean age 55.0 ± 12.0 years; 40% female; 23% with diabetes), deprivation status was linked with increased BMI and diabetes prevalence. 186 (74%) returned for the follow-up. Within this group, findings indicated associations between deprivation and lung abnormalities (p = 0.0085), coronary artery disease (p = 0.0128), and renal inflammation (p = 0.0421). Furthermore, patients with higher deprivation exhibited worse scores in health-related quality of life (EQ-5D-5L, p = 0.0084), illness perception (BIPQ, p = 0.0004), anxiety and depression levels (PHQ-4, p = 0.0038), and diminished physical activity (DASI, p = 0.002). At the 3-month mark, those with greater deprivation showed a higher frequency of referrals to secondary care due to ongoing COVID-19 symptoms (p = 0.0438). However, clinical outcomes were not influenced by deprivation. CONCLUSIONS: In a post-hospital COVID-19 population, socioeconomic deprivation was associated with impaired health status and secondary care episodes. Deprivation influences illness trajectory after COVID-19.

In our study, we aimed to understand how socioeconomic factors impact recovery from COVID-19 following hospitalisation. We followed 252 patients, collecting health data and utilising advanced imaging techniques. We discovered that individuals from deprived areas experienced more severe health complications, reported worse quality of life, and required more specialist care. However, their clinical outcomes were not significantly different. This underscores that socioeconomic deprivation affects health recovery, underlining the need for tailored care for these individuals. Our findings emphasise the importance of considering socioeconomic factors in recovery plans post-COVID-19, potentially improving healthcare for those in deprived areas.

Cardiovascular sequelae of trastuzumab and anthracycline in long-term survivors of breast cancer.

OBJECTIVES: Long-term follow-up of patients treated with trastuzumab largely focuses on those with reduced left ventricular ejection fraction (LVEF) on treatment completion. This study sought to evaluate the prevalence of cardiovascular risk factors, overt cardiovascular disease and cardiac imaging abnormalities using cardiac magnetic resonance (CMR), in participants with normal LVEF on completion of trastuzumab±anthracycline therapy at least 5 years previously. METHODS: Participants with human epidermal growth factor receptor 2-positive breast cancer treated with trastuzumab±anthracycline ≥5 years previously were identified from a clinical database. All participants had normal LVEF prior to, and on completion of, treatment. Participants underwent clinical cardiovascular evaluation, ECG, cardiac biomarker evaluation and CMR. Left ventricular systolic dysfunction (LVSD) was defined as LVEF <50%. RESULTS: Forty participants were recruited between 15 March 2021 and 19 July 2022. Median time since completion of trastuzumab was 7.8 years (range 5.9-10.8 years) and 90% received prior anthracycline. 25% of participants had LVSD; median LVEF was 55.2% (Q1-Q3, 51.3-61.2). 30% of participants had N-terminal pro-B-type natriuretic peptide >125 pg/mL and 8% had high-sensitivity cardiac troponin T >14 ng/L. 33% of participants had a new finding of hypertension. 58% had total cholesterol >5.0 mmol/L, 43% had triglycerides >1.7 mmol/L and 5% had a new diagnosis of diabetes. CONCLUSIONS: The presence of asymptomatic LVSD, abnormal cardiac biomarkers and cardiac risk factors in participants treated with trastuzumab and anthracycline at least 5 years previously is common, even in those with normal LVEF on completion of treatment. Our findings reinforce the relevance of comprehensive evaluation of cardiovascular risk factors following completion of cancer therapy, in addition to LVEF assessment.

Post-COVID-19 illness and associations with sex and gender.

BACKGROUND: Post-COVID-19 syndromes have associated with female sex, but the pathophysiological basis is uncertain. AIM: There are sex differences in myocardial inflammation identified using cardiac magnetic resonance (CMR) in post-COVID-19 patients, and in patient reported health outcomes following COVID-19 infection. DESIGN: This prospective study investigated the time-course of multiorgan injury in survivors of COVID-19 during convalescence. METHODS: Clinical information, blood biomarkers, and patient reported outcome measures were prospectively acquired at enrolment (visit 1) and 28-60 days post-discharge (visit 2). Chest computed tomography (CT) and CMR were performed at visit 2. Follow-up was carried out for serious adverse events, including death and rehospitalization. RESULTS: Sixty-nine (43%) of 159 patients recruited were female. During the index admission, females had a lower peak C-reactive protein (74 mg/l (21,163) versus 123 mg/l (70, 192) p = 0.008) and peak ferritin (229 µg/l (103, 551) versus 514 µg/l (228, 1122) p < 0.001). Using the Modified Lake-Louise criteria, females were more likely to have definite evidence of myocardial inflammation (54% (37/68) versus 33% (30/90) p = 0.003). At enrolment and 28-60 days post-discharge, enhanced illness perception, higher levels of anxiety and depression and lower predicted maximal oxygen utilization occurred more commonly in women. The mean (SD, range) duration of follow-up after hospital discharge was 450 (88) days (range 290, 627 days). Compared to men, women had lower rates of cardiovascular hospitalization (0% versus 8% (7/90); p = 0.018). CONCLUSIONS: Women demonstrated worse patient reported outcome measures at index admission and 28-60 days follow-up though cardiovascular hospitalization was lower.

StrainNet: Improved Myocardial Strain Analysis of Cine MRI by Deep Learning from DENSE.

Purpose: To develop a three-dimensional (two dimensions + time) convolutional neural network trained with displacement encoding with stimulated echoes (DENSE) data for displacement and strain analysis of cine MRI. Materials and Methods: In this retrospective multicenter study, a deep learning model (StrainNet) was developed to predict intramyocardial displacement from contour motion. Patients with various heart diseases and healthy controls underwent cardiac MRI examinations with DENSE between August 2008 and January 2022. Network training inputs were a time series of myocardial contours from DENSE magnitude images, and ground truth data were DENSE displacement measurements. Model performance was evaluated using pixelwise end-point error (EPE). For testing, StrainNet was applied to contour motion from cine MRI. Global and segmental circumferential strain (Ecc) derived from commercial feature tracking (FT), StrainNet, and DENSE (reference) were compared using intraclass correlation coefficients (ICCs), Pearson correlations, Bland-Altman analyses, paired t tests, and linear mixed-effects models. Results: The study included 161 patients (110 men; mean age, 61 years ± 14 [SD]), 99 healthy adults (44 men; mean age, 35 years ± 15), and 45 healthy children and adolescents (21 males; mean age, 12 years ± 3). StrainNet showed good agreement with DENSE for intramyocardial displacement, with an average EPE of 0.75 mm ± 0.35. The ICCs between StrainNet and DENSE and FT and DENSE were 0.87 and 0.72, respectively, for global Ecc and 0.75 and 0.48, respectively, for segmental Ecc. Bland-Altman analysis showed that StrainNet had better agreement than FT with DENSE for global and segmental Ecc. Conclusion: StrainNet outperformed FT for global and segmental Ecc analysis of cine MRI.Keywords: Image Postprocessing, MR Imaging, Cardiac, Heart, Pediatrics, Technical Aspects, Technology Assessment, Strain, Deep Learning, DENSE Supplemental material is available for this article. © RSNA, 2023.

Randomised trial of stable chest pain investigation: 3-year clinical and quality of life results from CE-MARC 2.

AIMS: Guidelines for suspected cardiac chest pain have used historical risk stratification tools, advocating invasive coronary angiography (ICA) first-line in those at highest risk. We aimed to determine whether different strategies to manage suspected stable angina affected medium-term cardiovascular event rates and patient-reported quality of life (QoL) measures. METHODS: CE-MARC 2, a three-arm parallel group trial, randomised patients with suspected stable cardiac chest pain and a Duke Clinical pretest likelihood of coronary artery disease between 10% and 90%. Patients were randomised to either first-line cardiovascular magnetic resonance (CMR), single-photon emission computed tomography (SPECT) or the UK National Institute for Health and Care Excellence (NICE) CG95 (2010) guidelines-directed care. For the three arms, 1-year and 3-year first major adverse cardiovascular event (MACE) rates and QoL assessed by the Seattle Angina Questionnaire, Short Form 12 (V.12) Questionnaire and EuroQol-5 Dimension Questionnaire were recorded. RESULTS: 1202 patients were randomised to CMR (n=481), SPECT (n=481) and NICE (n=240). Forty-two patients (18 CMR, 18 SPECT, 6 NICE) experienced one or more MACEs. The percentage rates (95% CIs) of MACE in the CMR, SPECT and NICE groups at 3 years were 3.7% (2.4%, 5.8%), 3.7% (2.4%, 5.8%) and 2.1% (0.9%, 4.8%), respectively. QoL scores did not significantly differ across domains. CONCLUSION: Despite a fourfold increase in referrals for ICA, the NICE CG95 (2010) guidelines risk-stratified care strategy did not significantly reduce 3-year MACE or improve QoL, as compared with functional imaging with CMR or SPECT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT01664858).

Intra-cardiac tumour and bicuspid aortic valve in a patient with neurofibromatosis type 1-rare associations: a case report.

Background: Neurofibromatosis (NF) is an autosomal dominant neurocutaneous disease with multi-system involvement. Three cardiovascular associations are recognized but infrequently reported: congenital heart disease, vasculopathy, and hypertension. Cardiac outflow tract pathology, pulmonary stenosis, and aortic co-arctation have been described in the literature with varying frequency. The incidence of intra-cardiac tumour is exceeding rare. Case summary: A 53-year-old man presented to the neurosurgical team with myelopathy secondary to cord compression arising from multiple cervical neurofibromas secondary to NF-1. Further cardiac evaluation with echocardiography and cardiac MRI uncovered the presence of both a bicuspid aortic valve (with mild aortic stenosis and moderate aortic regurgitation) and a concurrent intra-cardiac tumour of the mitral papillary muscle; a combined finding which was not reported previously. Serial evaluation confirmed stable disease with no major progression over time. Discussion: Our case highlights the importance of recognizing cardiovascular manifestations of NF-1 and instituting appropriate screening and surveillance strategies. Targeted non-invasive imaging strategies may be more suited for this purpose over routine clinical examination alone.

Vascular mechanisms of post-COVID-19 conditions: Rho-kinase is a novel target for therapy.

BACKGROUND: In post-coronavirus disease-19 (post-COVID-19) conditions (long COVID), systemic vascular dysfunction is implicated, but the mechanisms are uncertain, and the treatment is imprecise. METHODS AND RESULTS: Patients convalescing after hospitalization for COVID-19 and risk factor matched controls underwent multisystem phenotyping using blood biomarkers, cardiorenal and pulmonary imaging, and gluteal subcutaneous biopsy (NCT04403607). Small resistance arteries were isolated and examined using wire myography, histopathology, immunohistochemistry, and spatial transcriptomics. Endothelium-independent (sodium nitroprusside) and -dependent (acetylcholine) vasorelaxation and vasoconstriction to the thromboxane A2 receptor agonist, U46619, and endothelin-1 (ET-1) in the presence or absence of a RhoA/Rho-kinase inhibitor (fasudil), were investigated. Thirty-seven patients, including 27 (mean age 57 years, 48% women, 41% cardiovascular disease) 3 months post-COVID-19 and 10 controls (mean age 57 years, 20% women, 30% cardiovascular disease), were included. Compared with control responses, U46619-induced constriction was increased (P = 0.002) and endothelium-independent vasorelaxation was reduced in arteries from COVID-19 patients (P < 0.001). This difference was abolished by fasudil. Histopathology revealed greater collagen abundance in COVID-19 arteries {Masson's trichrome (MT) 69.7% [95% confidence interval (CI): 67.8-71.7]; picrosirius red 68.6% [95% CI: 64.4-72.8]} vs. controls [MT 64.9% (95% CI: 59.4-70.3) (P = 0.028); picrosirius red 60.1% (95% CI: 55.4-64.8), (P = 0.029)]. Greater phosphorylated myosin light chain antibody-positive staining in vascular smooth muscle cells was observed in COVID-19 arteries (40.1%; 95% CI: 30.9-49.3) vs. controls (10.0%; 95% CI: 4.4-15.6) (P < 0.001). In proof-of-concept studies, gene pathways associated with extracellular matrix alteration, proteoglycan synthesis, and viral mRNA replication appeared to be upregulated. CONCLUSION: Patients with post-COVID-19 conditions have enhanced vascular fibrosis and myosin light change phosphorylation. Rho-kinase activation represents a novel therapeutic target for clinical trials.

Image-based estimation of the left ventricular cavity volume using deep learning and Gaussian process with cardio-mechanical applications.

In this investigation, an image-based method has been developed to estimate the volume of the left ventricular cavity using cardiac magnetic resonance (CMR) imaging data. Deep learning and Gaussian processes have been applied to bring the estimations closer to the cavity volumes manually extracted. CMR data from 339 patients and healthy volunteers have been used to train a stepwise regression model that can estimate the volume of the left ventricular cavity at the beginning and end of diastole. We have decreased the root mean square error (RMSE) of cavity volume estimation approximately from 13 to 8 ml compared to the common practice in the literature. Considering the RMSE of manual measurements is approximately 4 ml on the same dataset, 8 ml of error is notable for a fully automated estimation method, which needs no supervision or user-hours once it has been trained. Additionally, to demonstrate a clinically relevant application of automatically estimated volumes, we inferred the passive material properties of the myocardium given the volume estimates using a well-validated cardiac model. These material properties can be further used for patient treatment planning and diagnosis.

Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study.

BACKGROUND: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. METHODS: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. RESULTS: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02). CONCLUSIONS: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: 58667920.

Pulmonary artery wave reflection and right ventricular function after lung resection.

BACKGROUND: Lung resection has been shown to impair right ventricular function. Although conventional measures of afterload do not change, surgical ligation of a pulmonary artery branch, as occurs during lobectomy, can create a unilateral proximal reflection site, increasing wave reflection (pulsatile component of afterload) and diverting blood flow through the contralateral pulmonary artery. We present a cardiovascular magnetic resonance imaging (MRI) observational cohort study of changes in wave reflection and right ventricular function after lung resection. METHODS: Twenty-seven patients scheduled for open lobectomy for suspected lung cancer underwent cardiovascular MRI preoperatively, on postoperative Day 2, and at 2 months. Wave reflection was assessed in the left and right pulmonary arteries (operative and non-operative, as appropriate) by wave intensity analysis and calculation of wave reflection index. Pulmonary artery blood flow distribution was calculated as percentage of total blood flow travelling in the non-operative pulmonary artery. Right ventricular function was assessed by ejection fraction and strain analysis. RESULTS: Operative pulmonary artery wave reflection increased from 4.3 (2.1-8.8) % preoperatively to 9.5 (4.9-14.9) % on postoperative Day 2 and 8.0 (2.3-11.7) % at 2 months (P<0.001) with an associated redistribution of blood flow towards the nonoperative pulmonary artery (r>0.523; P<0.010). On postoperative Day 2, impaired right ventricular ejection fraction was associated with increased operative pulmonary artery wave reflection (r=-0.480; P=0.028) and pulmonary artery blood flow redistribution (r=-0.545; P=0.011). At 2 months, impaired right ventricular ejection fraction and right ventricular strain were associated with pulmonary artery blood flow redistribution (r=-0.634, P=0.002; r=0.540, P=0.017). CONCLUSIONS: Pulsatile afterload increased after lung resection. The unilateral increase in operative pulmonary artery wave reflection resulted in redistribution of blood flow through the nonoperative pulmonary artery and was associated with right ventricular dysfunction. CLINICAL TRIAL REGISTRATION: NCT01892800.

NT-proBNP in patients presenting with myocardial infarction and non-obstructive coronary arteries without left ventricular systolic dysfunction.

Background: Myocardial infarction and non-obstructive coronary arteries (MINOCA) affects 1 in 9 patients with acute coronary syndrome and has no evidence-based therapy. NT-proBNP is an established biomarker associated with prognosis in heart failure and ischemic heart disease, although there is a paucity of data in patients with MINOCA. Methods: Prospective study of the diagnostic and clinical utility of measuring NT-proBNP in patients with MINOCA without left ventricular dysfunction or heart failure. Data collection was undertaken for patients with an initial diagnosis of MINOCA following urgent coronary angiography in the Golden Jubilee National Hospital (Clydebank, UK), a tertiary center. Demographics were collected in addition to left ventricular function by transthoracic echocardiography. NT-proBNP was measured from a clinically indicated blood sample obtained during routine venepuncture or within the catheter laboratory. Patient outcomes were collected prospectively by the clinical care team using digital follow-up. Results: Fifty-five patients with an initial diagnosis of MINOCA and left ventricular ejection fraction >40 % were included. NT-proBNP was available in 87 % of patients with a median value of 312 pg/mL (interquartile range: 107, 725). Post-discharge, 40 % (n = 24) of patients were readmitted to the hospital, including 15 with chest pain. NT-proBNP ≥125 pg/mL was associated with rehospitalization (P = 0.02). Two patients died and bleeding complications with concomitant antiplatelet therapy occurred in eight patients. Conclusion: NT-proBNP ≥ 125 pg/mL occurred in 72 % of patients presenting with MINOCA and an ejection fraction > 40% and was associated with rehospitalization.

Left ventricular dysfunction with preserved ejection fraction: the most common left ventricular disorder in chronic kidney disease patients.

Chronic kidney disease (CKD) is a risk factor for premature cardiovascular disease. As kidney function declines, the presence of left ventricular abnormalities increases such that by the time kidney replacement therapy is required with dialysis or kidney transplantation, more than two-thirds of patients have left ventricular hypertrophy. Historically, much research in nephrology has focussed on the structural and functional aspects of cardiac disease in CKD, particularly using echocardiography to describe these abnormalities. There is a need to translate knowledge around these imaging findings to clinical outcomes such as unplanned hospital admission with heart failure and premature cardiovascular death. Left ventricular hypertrophy and cardiac fibrosis, which are common in CKD, predispose to the clinical syndrome of heart failure with preserved left ventricular ejection fraction (HFpEF). There is a bidirectional relationship between CKD and HFpEF, whereby CKD is a risk factor for HFpEF and CKD impacts outcomes for patients with HFpEF. There have been major improvements in outcomes for patients with heart failure and reduced left ventricular ejection fraction as a result of several large randomized controlled trials. Finding therapy for HFpEF has been more elusive, although recent data suggest that sodium-glucose cotransporter 2 inhibition offers a novel evidence-based class of therapy that improves outcomes in HFpEF. These observations have emerged as this class of drugs has also become the standard of care for many patients with proteinuric CKD, suggesting that there is now hope for addressing the combination of HFpEF and CKD in parallel. In this review we summarize the epidemiology, pathophysiology, diagnostic strategies and treatment of HFpEF with a focus on patients with CKD.

Multisystem involvement in COVID-19: what have we learnt?

The COVID-19 illness trajectory involves persistent cardio-renal inflammation, activation of the haemostatic pathway and lung involvement. Results of a study carried out by the authors' team demonstrate a link between post-COVID-19 syndrome (people who have long COVID) and multisystem disease, which partly explains the lingering impairments in patient-reported health-related quality of life, physical function and psychological wellbeing after COVID-19. This article discusses what hospital physicians need to be aware of when considering the likelihood of myocarditis in patients with post-COVID-19 syndrome and the implications in the longer term.

A multisystem, cardio-renal investigation of post-COVID-19 illness.

The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607 ). Serial blood biomarkers, digital electrocardiography and patient-reported outcome measures were obtained in-hospital and at 28-60 days post-discharge when multisystem imaging using chest computed tomography with pulmonary and coronary angiography and cardio-renal magnetic resonance imaging was also obtained. Longer-term clinical outcomes were assessed using electronic health records. Compared to controls (n = 29), at 28-60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was 'very likely' in 21 (13%) patients, 'probable' in 65 (41%) patients, 'unlikely' in 56 (35%) patients and 'not present' in 17 (11%) patients. At 28-60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01). During follow-up (mean, 450 days), 24 (15%) patients and two (7%) controls died or were rehospitalized, and 108 (68%) patients and seven (26%) controls received outpatient secondary care (P = 0.017). The illness trajectory of patients after hospitalization with COVID-19 includes persisting multisystem abnormalities and health impairments that could lead to substantial demand on healthcare services in the future.

Inhibition of myocardial cathepsin-L release during reperfusion following myocardial infarction improves cardiac function and reduces infarct size.

AIMS: Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevation myocardial infarction (STEMI) to heart failure. Here, we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury. METHODS AND RESULTS: We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 h post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis. CONCLUSION: Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.