Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced electrocardiogram analysis.

AIMS: Typical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. The ECG is used as the gatekeeper to cardiac imaging for diagnosis. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM. METHODS AND RESULTS: Advanced ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM [n = 75 overt, n = 32 relative (<15 mm hypertrophy); a subgroup of which underwent cardiovascular magnetic resonance (n = 92)], and comparator subjects (n = 2449), including healthy volunteers (n = 1672), patients with coronary artery disease (n = 372), left ventricular electrical remodelling (n = 108), ischaemic (n = 114) or non-ischaemic cardiomyopathy (n = 57), and asymmetrical septal hypertrophy HCM (n = 126). Multivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy [area under the receiver operating characteristic (AUC) curve (bootstrapped 95% confidence interval) 0.982 (0.965-0.993)]. Linear discriminant analysis also diagnosed ApHCM with high accuracy [AUC 0.989 (0.986-0.991)]. CONCLUSION: Explainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting that future diagnostic and management strategies may incorporate both features.

Improved reproducibility for myocardial ASL: Impact of physiological and acquisition parameters.

PURPOSE: To investigate and mitigate the influence of physiological and acquisition-related parameters on myocardial blood flow (MBF) measurements obtained with myocardial Arterial Spin Labeling (myoASL). METHODS: A Flow-sensitive Alternating Inversion Recovery (FAIR) myoASL sequence with bSSFP and spoiled GRE (spGRE) readout is investigated for MBF quantification. Bloch-equation simulations and phantom experiments were performed to evaluate how variations in acquisition flip angle (FA), acquisition matrix size (AMS), heart rate (HR) and blood T 1 $$ {\mathrm{T}}_1 $$ relaxation time ( T 1 , B $$ {\mathrm{T}}_{1,B} $$ ) affect quantification of myoASL-MBF. In vivo myoASL-images were acquired in nine healthy subjects. A corrected MBF quantification approach was proposed based on subject-specific T 1 , B $$ {\mathrm{T}}_{1,B} $$ values and, for spGRE imaging, subtracting an additional saturation-prepared baseline from the original baseline signal. RESULTS: Simulated and phantom experiments showed a strong dependence on AMS and FA ( R 2 $$ {R}^2 $$ >0.73), which was eliminated in simulations and alleviated in phantom experiments using the proposed saturation-baseline correction in spGRE. Only a very mild HR dependence ( R 2 $$ {R}^2 $$ >0.59) was observed which was reduced when calculating MBF with individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ . For corrected spGRE, in vivo mean global spGRE-MBF ranged from 0.54 to 2.59 mL/g/min and was in agreement with previously reported values. Compared to uncorrected spGRE, the intra-subject variability within a measurement (0.60 mL/g/min), between measurements (0.45 mL/g/min), as well as the inter-subject variability (1.29 mL/g/min) were improved by up to 40% and were comparable with conventional bSSFP. CONCLUSION: Our results show that physiological and acquisition-related factors can lead to spurious changes in myoASL-MBF if not accounted for. Using individual T 1 , B $$ {\mathrm{T}}_{1,B} $$ and a saturation-baseline can reduce these variations in spGRE and improve reproducibility of FAIR-myoASL against acquisition parameters.

Predictors of outcome in patients with moderate mixed aortic valve disease.

OBJECTIVES: Grading the severity of moderate mixed aortic stenosis and regurgitation (MAVD) is challenging and the disease poorly understood. Identifying markers of haemodynamic severity will improve risk stratification and potentially guide timely treatment. This study aims to identify prognostic haemodynamic markers in patients with moderate MAVD. METHODS: Moderate MAVD was defined as coexisting moderate aortic stenosis (aortic valve area (AVA) 1.0-1.5 cm2) and moderate aortic regurgitation (vena contracta (VC) 0.3-0.6 cm). Consecutive patients diagnosed between 2015 and 2019 were included from a multicentre registry. The primary composite outcome of death or heart failure hospitalisation was evaluated among these patients. Demographics, comorbidities, echocardiography and treatment data were assessed for their prognostic significance. RESULTS: 207 patients with moderate MAVD were included, aged 78 (66-84) years, 56% male sex, AVA 1.2 (1.1-1.4) cm2 and VC 0.4 (0.4-0.5) cm. Over a follow-up of 3.5 (2.5-4.7) years, the composite outcome was met in 89 patients (43%). Univariable associations with the primary outcome included older age, previous myocardial infarction, previous cerebrovascular event, atrial fibrillation, New York Heart Association >2, worse renal function, tricuspid regurgitation ≥2 and mitral regurgitation ≥2. Markers of biventricular systolic function, cardiac remodelling and transaortic valve haemodynamics demonstrated an inverse association with the primary composite outcome. In multivariable analysis, peak aortic jet velocity (Vmax) was independently and inversely associated with the composite outcome (HR: 0.63, 95% CI 0.43 to 0.93; p=0.021) in an adjusted model along with age (HR: 1.05, 95% CI 1.03 to 1.08; p<0.001), creatinine (HR: 1.002, 95% CI 1.001 to 1.003; p=0.005), previous cerebrovascular event (85% vs 42%; HR: 3.04, 95% CI 1.54 to 5.99; p=0.001) and left ventricular ejection fraction (LVEF) (HR: 0.97, 95% CI 0.95 to 0.99; p=0.007). Patients with Vmax ≤2.8 m/s and LVEF ≤50% (n=27) had the worst outcome compared with the rest of the population (72% vs 41%; HR: 3.87, 95% CI 2.20 to 6.80; p<0.001). CONCLUSIONS: Patients with truly moderate MAVD have a high incidence of death and heart failure hospitalisation (43% at 3.5 (2.5-4.7) years). Within this group, a high-risk group characterised by disproportionately low aortic Vmax (≤2.8 m/s) and adverse remodelling (LVEF ≤50%) have the worst outcomes.

Innovative approach to medical leadership and management development: clinician secondment to a management consulting firm.

BACKGROUND AND AIM: Opportunities to participate in leadership and management with protected time can be limited for clinical trainees. The aim of this fellowship was to gain experience of gold standard healthcare management by becoming part of multidisciplinary teams working to deliver transformational change in the National Health Service (NHS). METHODS: A 6-month pilot fellowship, structured as an Out of Programme Experience was created for two registrars to be seconded to the healthcare division of Deloitte, a leading professional services firm. Competitive selection was jointly administered by the Director of Medical Education at St Bartholomew's Hospital and Deloitte. RESULTS: The successful candidates worked on service-led and digital transformation projects, interfacing with senior NHS executives and directors. Trainees gained direct experience and understanding of high-level decision making in the NHS, tackling complex service delivery problems and the practical realities of delivering change within a constrained budget. One impact of this pilot has been completion of a business case to scale up the fellowship into an established programme that can allow other trainees to apply. CONCLUSION: This innovative fellowship has allowed interested trainees an opportunity to broaden the relevant skills and experience in leadership and management required in specialty training curriculum with real-life application in the NHS.

Heart failure and excess mortality after aortic valve replacement in aortic stenosis.

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.

Evaluation of Microvascular Rarefaction in Vascular Cognitive Impairment and Heart Failure (CRUCIAL): Study Protocol for an Observational 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.

Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.

BACKGROUND: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037). CONCLUSIONS: Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

Myocardial Approximate Spin-lock Dispersion Mapping using a Simultaneous T2 and TRAFF2 Mapping at 3T MRI.

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Myocardial infarction (MI) represents a third of all IHD cases, and cardiac magnetic resonance imaging (MRI) is often used to assess its damage to myocardial viability. Late gadolinium enhancement (LGE) is the current gold standard, but the use of gadolinium-based agents limits the clinical applicability in some patients. Spin-lock (SL) dispersion has recently been proposed as a promising non-contrast biomarker for the assessment of MI. However, at 3T, the required range of SL preparations acquired at different amplitudes suffers from specific absorption rate (SAR) limitations and off-resonance artifacts. Relaxation Along a Fictitious Field (RAFF) is an alternative to SL preparations with lower SAR requirements, while still sampling relaxation in the rotating frame. In this study, a single breath-hold simultaneous TRAFF2 and T2 mapping sequence is proposed for SL dispersion mapping at 3T. Excellent reproducibility (coefficient of variations lower than 10%) was achieved in phantom experiments, indicating good intrascan repeatability. The average myocardial TRAFF2, T2, and SL dispersion obtained with the proposed sequence (68.0±10.7 ms, 44.0±4.0 ms, and 0.4±0.2 ×10-4 s2, respectively) were comparable to the reference methods (62.7±11.7 ms, 41.2±2.4 ms, and 0.3±0.2x 10-4s2, respectively). High visual map quality, free of B0 and B1+ related artifacts, for T2, TRAFF2, and SL dispersion maps were obtained in phantoms and in vivo, suggesting promise in clinical use at 3T. Clinical relevance - and imaging promises non-contrast assessment of scar and focal fibrosis in a single breath-hold using approximate spin-lock dispersion mapping.

Preprocedural Prognostic Factors in Acute Decompensated Aortic Stenosis.

Acute decompensated aortic stenosis (ADAS) is common and associated with poor outcomes. Myocardial remodeling and function, including a novel echo staging classification (0 to 4, representing increasing degrees of cardiac damage/dysfunction), impact outcomes in stable aortic stenosis. However, this has not been assessed in patients with ADAS. This study aims to evaluate the impact of the myocardium, echo staging classification, and clinical parameters on mortality in ADAS. ADAS was defined as an acute deterioration in symptoms (New York Heart Association 4, Canadian Cardiovascular Society 3/4, or syncope) that warranted admission to the hospital and urgent aortic valve replacement. Using a retrospective observational study design, 292 consecutive patients with ADAS who underwent transcatheter aortic valve implantation (TAVI) were identified and included in this study. Echocardiographic and clinical characteristics were evaluated using regression analysis. The outcome was all-cause mortality after TAVI. At 1 year after TAVI, advanced echo staging (>2) independently predicted mortality (hazards ratio: 1.85, 95% confidence interval: 1.01 to 3.39; p = 0.045). At a follow-up of 2.4 ± 1.4 years, myocardial, valvular, and clinical parameters did not predict mortality, except for frailty (hazards ratio: 2.31, 95% confidence interval: 1.38 to 3.85; p = 0.001). In patients with ADAS, short-term mortality after TAVI is influenced by more advanced cardiac damage/dysfunction based on the echo staging classification, whereas mid-term mortality is driven by frailty rather than echo staging classification.

Association of Myocardial Fibrosis and Stroke Volume by Cardiovascular Magnetic Resonance in Patients With Severe Aortic Stenosis With Outcome After Valve Replacement: The British Society of Cardiovascular Magnetic Resonance AS700 Study.

Importance: Low-flow severe aortic stenosis (AS) has higher mortality than severe AS with normal flow. The conventional definition of low-flow AS is an indexed stroke volume (SVi) by echocardiography less than 35 mL/m2. Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying left ventricular volumes and function from which SVi by CMR can be derived. Objective: To determine the association of left ventricular SVi by CMR with myocardial remodeling and survival among patients with severe AS after valve replacement. Design, Setting, and Participants: This multicenter longitudinal cohort study was conducted between January 2003 and May 2015 across 6 UK cardiothoracic centers. Patients with severe AS listed for either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) were included. Patients underwent preprocedural echocardiography and CMR. Patients were stratified by echocardiography-derived aortic valve mean and/or peak gradient and SVi by CMR into 4 AS endotypes: low-flow, low-gradient AS; low-flow, high-gradient AS; normal-flow, low-gradient AS; and normal-flow, high-gradient AS. Patients were observed for a median of 3.6 years. Data were analyzed from September to November 2021. Exposures: SAVR or TAVR. Main Outcomes and Measures: All-cause and cardiovascular (CV) mortality after aortic valve intervention. Results: Of 674 included patients, 425 (63.1%) were male, and the median (IQR) age was 75 (66-80) years. The median (IQR) aortic valve area index was 0.4 (0.3-0.4) cm2/m2. Patients with low-flow AS endotypes (low gradient and high gradient) had lower left ventricular ejection fraction, mass, and wall thickness and increased all-cause and CV mortality than patients with normal-flow AS (all-cause mortality: hazard ratio [HR], 2.08; 95% CI, 1.37-3.14; P < .001; CV mortality: HR, 3.06; 95% CI, 1.79-5.25; P < .001). CV mortality was independently associated with lower SVi (HR, 1.64; 95% CI, 1.08-2.50; P = .04), age (HR, 2.54; 95% CI, 1.29-5.01; P = .001), and higher quantity of late gadolinium enhancement (HR, 2.93; 95% CI, 1.68-5.09; P < .001). CV mortality hazard increased more rapidly in those with an SVI less than 45 mL/m2. SVi by CMR was independently associated with age, atrial fibrillation, focal scar (by late gadolinium enhancement), and parameters of cardiac remodeling (left ventricular mass and left atrial volume). Conclusions and Relevance: In this cohort study, SVi by CMR was associated with CV mortality after aortic valve replacement, independent of age, focal scar, and ejection fraction. The unique capability of CMR to quantify myocardial scar, combined with other prognostically important imaging biomarkers, such as SVi by CMR, may enable comprehensive stratification of postoperative risk in patients with severe symptomatic AS.

Aortic regurgitation management: a systematic review of clinical practice guidelines and recommendations.

Guidelines for the diagnosis and management of aortic regurgitation (AR) contain recommendations that do not always match. We systematically reviewed clinical practice guidelines and summarized similarities and differences in the recommendations as well as gaps in evidence on the management of AR. We searched MEDLINE and Embase (1 January 2011 to 1 September 2021), Google Scholar, and websites of relevant organizations for contemporary guidelines that were rigorously developed as assessed by the Appraisal of Guidelines for Research and Evaluation II tool. Three guidelines met our inclusion criteria. There was consensus on the definition of severe AR and use of echocardiography and of multimodality imaging for diagnosis, with emphasis on comprehensive assessment by the heart valve team to assess suitability and choice of intervention. Surgery is indicated in all symptomatic patients and aortic valve replacement is the cornerstone of treatment. There is consistency in the frequency of follow-up of patients, and safety of non-cardiac surgery in patients without indications for surgery. Discrepancies exist in recommendations for 3D imaging and the use of global longitudinal strain and biomarkers. Cut-offs for left ventricular ejection fraction and size for recommending surgery in severe asymptomatic AR also vary. There are no specific AR cut-offs for high-risk surgery and the role of percutaneous intervention is yet undefined. Recommendations on the treatment of mixed valvular disease are sparse and lack robust prospective data.

Mechanical thrombectomy with retrievable stents and aspiration catheters for acute ischaemic stroke: a meta-analysis of randomised controlled trials.

BACKGROUND: Retrievable stents and aspiration catheters have been developed to provide more effective arterial recanalisation in acute ischaemic stroke. AIMS: The aim of this analysis was to test the effect of mechanical thrombectomy on mortality and long-term neurological outcome in patients presenting with acute large-vessel anterior circulation ischaemic stroke. METHODS: A structured search identified randomised controlled trials of thrombectomy (using a retrievable stent or aspiration catheter) versus control on a background of medical therapy which included intravenous thrombolysis if appropriate. The primary endpoint was disability at 90-day follow-up as assessed by the modified Rankin scale (mRS). Secondary endpoints included all-cause mortality and symptomatic intracranial haemorrhage. A Bayesian mixed-effects model was used for analysis. RESULTS: Twelve trials met the inclusion criteria, comprising a total of 1,276 patients randomised to thrombectomy and 1,282 patients to control. Randomisation to thrombectomy significantly reduced disability at 90 days (odds ratio [OR] 0.52, 95% credible interval [CrI] 0.46 to 0.61, probability(control better)<0.0001). Furthermore, thrombectomy reduced the odds of functional dependence at 90 days, indicated by an mRS score >2 (OR 0.44, CrI 0.37 to 0.52, p<0.0001). Thrombectomy reduced all-cause mortality at 90 days (16.1% vs 19.2%, OR 0.81, 95% CrI 0.66 to 0.99, p=0.024). The frequency of symptomatic intracranial haemorrhage was similar between thrombectomy (4.2%) and control (4.0%) (OR 1.12, 95% CrI 0.76 to 1.68, p=0.72). CONCLUSIONS: In patients with an acute anterior circulation stroke, modern device thrombectomy significantly reduces death and subsequent disability. The magnitude of these effects suggests that universal access to this treatment strategy should be the standard of care.

Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis.

OBJECTIVE: The coexistence of wild-type transthyretin cardiac amyloidosis (ATTR) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). However, the impact of ATTR and AS on the resultant AS-ATTR is unclear and poses diagnostic and management challenges. We therefore used a multicohort approach to evaluate myocardial structure, function, stress and damage by assessing age-related, afterload-related and amyloid-related remodelling on the resultant AS-ATTR phenotype. METHODS: We compared four samples (n=583): 359 patients with AS, 107 with ATTR (97% Perugini grade 2), 36 with AS-ATTR (92% Perugini grade 2) and 81 age-matched and ethnicity-matched controls. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy was used to diagnose amyloidosis (Perugini grade 1 was excluded). The primary end-point was NT-pro Brain Natriuretic Peptide (BNP) and secondary end-points related to myocardial structure, function and damage. RESULTS: Compared with older age controls, the three disease cohorts had greater cardiac remodelling, worse function and elevated NT-proBNP/high-sensitivity Troponin-T (hsTnT). NT-proBNP was higher in AS-ATTR (2844 (1745, 4635) ng/dL) compared with AS (1294 (1077, 1554)ng/dL; p=0.002) and not significantly different to ATTR (3272 (2552, 4197) ng/dL; p=0.63). Diastology, hsTnT and prevalence of carpal tunnel syndrome were statistically similar between AS-ATTR and ATTR and higher than AS. The left ventricular mass indexed in AS-ATTR was lower than ATTR (139 (112, 167) vs 180 (167, 194) g; p=0.013) and non-significantly different to AS (120 (109, 130) g; p=0.179). CONCLUSIONS: The AS-ATTR phenotype likely reflects an early stage of amyloid infiltration, but the combined insult resembles ATTR. Even after treatment of AS, ATTR-specific therapy is therefore likely to be beneficial.

Myocardial Perfusion Imaging After Severe COVID-19 Infection Demonstrates Regional Ischemia Rather Than Global Blood Flow Reduction.

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis. Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients. Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF. Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54-71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29-146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01). Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.

Prospective Case-Control Study of Cardiovascular Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers.

OBJECTIVES: The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome-coronavirus-2 infection. BACKGROUND: Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease. METHODS: Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157). At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers). Analysis was blinded, using objective artificial intelligence analytics where available. RESULTS: A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited. Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days). Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide). With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal). These were distributed equally between seropositive and seronegative individuals. CONCLUSIONS: Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome-coronavirus-2 infection.

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis.

BACKGROUND: Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR). OBJECTIVES: This study identified clinical characteristics and outcomes of AS-CA compared with lone AS. METHODS: Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality. RESULTS: A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36). CONCLUSIONS: Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.