Severe mental illness: cardiovascular risk assessment and management.

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI.

The Effect of a Neuronal Nitric Oxide Synthase Inhibitor on Neurovascular Regulation in Humans.

BACKGROUND: Neurovascular coupling (NVC) is a key process in cerebral blood flow regulation. NVC ensures adequate brain perfusion to changes in local metabolic demands. Neuronal nitric oxide synthase (nNOS) is suspected to be involved in NVC; however, this has not been tested in humans. Our objective was to investigate the effects of nNOS inhibition on NVC in humans. METHODS: We performed a 3-visit partially randomized, double-blinded, placebo-controlled, crossover study in 12 healthy subjects. On each visit, subjects received an intravenous infusion of either S-methyl-L-thiocitrulline (a selective nNOS-inhibitor), 0.9% saline (placebo control), or phenylephrine (pressor control). The NVC assessment involved eliciting posterior circulation hyperemia through visual stimulation while measuring posterior and middle cerebral arteries blood velocity. RESULTS: nNOS inhibition blunted the rapidity of the NVC response versus pressor control, evidenced by a reduced initial rise in mean posterior cerebral artery velocity (-3.3% [-6.5, -0.01], P=0.049), and a reduced rate of increase (ie, acceleration) in posterior cerebral artery velocity (slope reduced -4.3% [-8.5, -0.1], P=0.045). The overall magnitude of posterior cerebral artery response relative to placebo control or pressor control was not affected. Changes in BP parameters were well-matched between the S-methyl-L-thiocitrulline and pressor control arms. CONCLUSIONS: Neuronal NOS plays a role in dynamic cerebral blood flow control in healthy adults, particularly the rapidity of the NVC response to visual stimulation. This work opens the way to further investigation of the role of nNOS in conditions of impaired NVC, potentially revealing a therapeutic target.

Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data.

BACKGROUND: Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. METHODS: 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. RESULTS: Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p < 0.001). Phenogroup membership significantly improved survival prediction compared to conventional factors. Phenogroups were not predictive of hospitalisation for HF. CONCLUSIONS: Applying unsupervised machine learning to routinely collected electronic health record data identified phenogroups with distinct clinical characteristics and unique survival profiles.

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential.

Nitric oxide (NO) plays an important and diverse signalling role in the cardiovascular system, contributing to the regulation of vascular tone, endothelial function, myocardial function, haemostasis, and thrombosis, amongst many other roles. NO is synthesised through the nitric oxide synthase (NOS)-dependent L-arginine-NO pathway, as well as the nitrate-nitrite-NO pathway. The three isoforms of NOS, namely neuronal (NOS1), inducible (NOS2), and endothelial (NOS3), have different localisation and functions in the human body, and are consequently thought to have differing pathophysiological roles. Furthermore, as we continue to develop a deepened understanding of the different roles of NOS isoforms in disease, the possibility of therapeutically modulating NOS activity has emerged. Indeed, impaired (or dysfunctional), as well as overactive (or dysregulated) NOS activity are attractive therapeutic targets in cardiovascular disease. This review aims to describe recent advances in elucidating the physiological role of NOS isoforms within the cardiovascular system, as well as mechanisms of dysfunctional and dysregulated NOS in cardiovascular disease. We then discuss the modulation of NO and NOS activity as a target in the development of novel cardiovascular therapeutics.

COVID-19 and the heart.

BACKGROUND: There is evidence for a bi-directional relationship between COVID-19 and the cardiovascular (CV) system. SOURCE OF DATA: Published literature. AREAS OF AGREEMENT: Pre-existing heart failure (HF) increases the risk of mortality with COVID-19. CV complications are recognized, including increased rates of acute coronary syndromes, HF, arrhythmia and myocarditis. Drugs targeting the angiotensin system are safe and may provide prognostic benefit. AREAS OF CONTROVERSY: Vaccination as a cause of myocarditis remains a key area of contention. GROWING POINTS: As the pandemic progresses, we are gaining more data about the long-term effects of COVID-19 on the CV system: long COVID, and medium-to-long-term increases in CV risk. AREAS TIMELY FOR DEVELOPING RESEARCH: Large-scale longitudinal studies will shed light on long-term CV outcomes with COVID-19. Furthermore, the differential effects of COVID-19 variants on the CV system must be investigated.

Diagnostic signature for heart failure with preserved ejection fraction (HFpEF): a machine learning approach using multi-modality electronic health record data.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is thought to be highly prevalent yet remains underdiagnosed. Evidence-based treatments are available that increase quality of life and decrease hospitalization. We sought to develop a data-driven diagnostic model to predict from electronic health records (EHR) the likelihood of HFpEF among patients with unexplained dyspnea and preserved left ventricular EF. METHODS AND RESULTS: The derivation cohort comprised patients with dyspnea and echocardiography results. Structured and unstructured data were extracted using an automated informatics pipeline. Patients were retrospectively diagnosed as HFpEF (cases), non-HF (control cohort I), or HF with reduced EF (HFrEF; control cohort II). The ability of clinical parameters and investigations to discriminate cases from controls was evaluated by extreme gradient boosting. A likelihood scoring system was developed and validated in a separate test cohort. The derivation cohort included 1585 consecutive patients: 133 cases of HFpEF (9%), 194 non-HF cases (Control cohort I) and 1258 HFrEF cases (Control cohort II). Two HFpEF diagnostic signatures were derived, comprising symptoms, diagnoses and investigation results. A final prediction model was generated based on the averaged likelihood scores from these two models. In a validation cohort consisting of 269 consecutive patients [with 66 HFpEF cases (24.5%)], the diagnostic power of detecting HFpEF had an AUROC of 90% (P < 0.001) and average precision of 74%. CONCLUSION: This diagnostic signature enables discrimination of HFpEF from non-cardiac dyspnea or HFrEF from EHR and can assist in the diagnostic evaluation in patients with unexplained dyspnea. This approach will enable identification of HFpEF patients who may then benefit from new evidence-based therapies.

Direct cardiac versus systemic effects of inorganic nitrite on human left ventricular function.

Inorganic nitrite is a source of nitric oxide (NO) and is considered as a potential therapy in settings where endogenous NO bioactivity is reduced and left ventricular (LV) function impaired. However, the effects of nitrite on human cardiac contractile function, and the extent to which these are direct or indirect, are unclear. We studied 40 patients undergoing diagnostic cardiac catheterization who had normal LV systolic function and were not found to have obstructive coronary disease. They received either an intracoronary sodium nitrite infusion (8.7-26 µmol/min, n = 20) or an intravenous sodium nitrite infusion (50 µg/kg/min, n = 20). LV pressure-volume relations were recorded. The primary end point was LV end-diastolic pressure (LVEDP). Secondary end points included indices of LV systolic and diastolic function. Intracoronary nitrite infusion induced a significant reduction in LVEDP, LV end-diastolic pressure-volume relationship (EDPVR), and the time to LV end-systole (LVEST) but had no significant effect on LV systolic function or systemic hemodynamics. Intravenous nitrite infusion induced greater effects, with significant decreases in LVEDP, EDPVR, LVEST, LV dP/dtmin, tau, and mean arterial pressure. Inorganic nitrite has modest direct effects on human LV diastolic function, independent of LV loading conditions and without affecting LV systolic properties. However, the systemic administration of nitrite has larger effects on LV diastolic function, which are related to reduction in both preload and afterload. These contractile effects of inorganic nitrite may indicate a favorable profile for conditions characterized by LV diastolic dysfunction.NEW & NOTEWORTHY This is the first study to assess the direct and indirect effects of inorganic nitrite on invasive measures of left ventricular function in humans in vivo. Inorganic nitrite has a modest direct myocardial effect, improving diastolic function. Systemic administration of nitrite has larger effects related to alterations in cardiac preload and afterload. The changes induced by nitrite appear favorable for potential use in conditions characterized by LV diastolic dysfunction.

Evaluation and improvement of the National Early Warning Score (NEWS2) for COVID-19: a multi-hospital study.

BACKGROUND: The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. METHODS: Training cohorts comprised 1276 patients admitted to King's College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy's and St Thomas' Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. RESULTS: A baseline model of 'NEWS2 + age' had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. CONCLUSIONS: NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.

Grapefruit juice enhances the systolic blood pressure-lowering effects of dietary nitrate-containing beetroot juice.

AIMS: Dietary nitrate from sources such as beetroot juice lowers blood pressure (BP) via the nitrate-nitrite-nitric oxide (NO) pathway. However, NO and nitrite are inactivated via reoxidation to nitrate, potentially limiting their activity. Cytochrome P450-3A4 inhibition with troleandomycin prevents nitrite re-oxidation to nitrate in rodent liver. Grapefruit juice contains the CYP3A4 inhibitor furanocoumarin. We therefore hypothesized that grapefruit juice would enhance BP-lowering with beetroot juice by maintaining circulating [nitrite]. METHODS: We performed a randomized, placebo-controlled, 7-hour crossover study in 11 healthy volunteers, attending on 3 occasions, receiving: a 70-mL shot of active beetroot juice (Beet-It) and either (i) 250 mL grapefruit juice (Active Beet+GFJ), or (ii) 250 mL water (Buxton, Active Beet+H2 O); or (iii) Placebo Beet+GFJ. RESULTS: The addition of grapefruit juice to active beetroot juice lowered systolic BP (SBP): Active Beet+GFJ vs Active Beet+H2 O (P = .02), and pulse pressure, PP (P = .0003). Peak mean differences in SBP and PP were seen at T = 5 hours: -3.3 mmHg (95% confidence interval [CI] -6.43 to -0.15) and at T = 2.5 hours: -4.2 mmHg (95% CI -0.3 to -8.2), respectively. Contrary to the hypothesis, plasma [nitrite] was lower with Active Beet+GFJ vs Active Beet+H2 O (P = .006), as was salivary nitrite production (P = .002) and saliva volume (-0.34 mL/min [95% CI -0.05 to -0.68]). The taste score of Beet+GFJ was 1.4/10 points higher than Beet+H2 O (P = .03). CONCLUSION: Grapefruit juice enhanced beetroot juice's effect on lowering SBP and PP despite decreasing plasma [nitrite]. Besides suggesting more complex mechanisms, there is potential for maximising the clinical benefit of dietary nitrate and targeting isolated systolic hypertension.

Pre-existing cardiovascular disease rather than cardiovascular risk factors drives mortality in COVID-19.

BACKGROUND: The relative association between cardiovascular (CV) risk factors, such as diabetes and hypertension, established CV disease (CVD), and susceptibility to CV complications or mortality in COVID-19 remains unclear. METHODS: We conducted a cohort study of consecutive adults hospitalised for severe COVID-19 between 1st March and 30th June 2020. Pre-existing CVD, CV risk factors and associations with mortality and CV complications were ascertained. RESULTS: Among 1721 patients (median age 71 years, 57% male), 349 (20.3%) had pre-existing CVD (CVD), 888 (51.6%) had CV risk factors without CVD (RF-CVD), 484 (28.1%) had neither. Patients with CVD were older with a higher burden of non-CV comorbidities. During follow-up, 438 (25.5%) patients died: 37% with CVD, 25.7% with RF-CVD and 16.5% with neither. CVD was independently associated with in-hospital mortality among patients < 70 years of age (adjusted HR 2.43 [95% CI 1.16-5.07]), but not in those ≥ 70 years (aHR 1.14 [95% CI 0.77-1.69]). RF-CVD were not independently associated with mortality in either age group (< 70 y aHR 1.21 [95% CI 0.72-2.01], ≥ 70 y aHR 1.07 [95% CI 0.76-1.52]). Most CV complications occurred in patients with CVD (66%) versus RF-CVD (17%) or neither (11%; p < 0.001). 213 [12.4%] patients developed venous thromboembolism (VTE). CVD was not an independent predictor of VTE. CONCLUSIONS: In patients hospitalised with COVID-19, pre-existing established CVD appears to be a more important contributor to mortality than CV risk factors in the absence of CVD. CVD-related hazard may be mediated, in part, by new CV complications. Optimal care and vigilance for destabilised CVD are essential in this patient group. Trial registration n/a.

Demographic, Behavioral, and Proximal Risk Factors for Gambling Disorder in the US Military.

BACKGROUND AND OBJECTIVES: To estimate the diagnostic prevalence and incidence of gambling disorder among United States service members and to identify associated risk factors, including demographics, history of mental illness or substance misuse, and proximity to legalized gambling vicinities. METHODS: Gambling disorder cases comprised active component Service members who received a pathological or problem gambling diagnosis between October 1, 2005 and September 30, 2015. There were 901 cases (392 incidents) during the study period. Controls were matched on the case military entrance date (N = 43,564). Geospatial distance between gambling venue and military treatment facilities were calculated, then multivariable logistic regression and survival analyses were conducted. RESULTS: The 10-year prevalence of gambling disorder was 6.6 per 100,000. Men were 3.5 times more likely than women to receive a gambling disorder diagnosis. Other risk factors included age over 24, Asian or Black race, formerly married, and enlisted rank. The odds of gambling disorder increased with duration and proximity to gambling venues, ranging from 2.0 to 3.9. Service members with prior substance misuse or mental health conditions were 3.9 times and 6.3 times more likely to receive a disordered gambling diagnosis than those without substance misuse or mental illness history, respectively. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The results of this study reveal that proximity to gambling venues and slot machines on bases, as well as a history of substance misuse or mental disorders, are important risk factors for gambling disorder in the US military. Department of Defense screening policies that focus on high-risk populations are appropriate. (Am J Addict 2021;00:00-00).

Establishing an Evidence Synthesis Capability For Psychological Health Topics in the Military Health System.

BACKGROUND: To promote evidence-based health care, clinical providers and decision makers rely on scientific evidence to inform best practices. Evidence synthesis (ES) is a key component of this process that serves to inform health care decisions by integrating and contextualizing research findings across studies. OBJECTIVE: This paper describes the process of establishing an ES capability in the Military Health System dedicated to psychological health topics. RESEARCH DESIGNS: The goal of establishing the current ES capability was to facilitate evidence-based decision-making among clinicians, clinic managers, research funders, and policymakers, through the production and dissemination of trustworthy ES reports. We describe how we developed this capability, provide an overview of the types of evidence syntheses products we use to respond to different stakeholders, and detail the procedures established for selecting and prioritizing synthesis topics. RESULTS: We report on the productivity, acceptability, and impact of our efforts. Our reports were used by a variety of stakeholders and working groups, briefed to major committees, included in official reports and policies, and cited in clinical practice guidelines and the peer-reviewed literature. CONCLUSIONS: Our experiences thus far suggest that the current ES capability offers a needed service within our health system. Our framework may help inform other agencies interested in developing or sponsoring a similar capability.

The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase.

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion (P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% (P = 0.02) and 0.5 ± 2.8% (P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress (r2 = -0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels.NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/.

The associations of opioid and benzodiazepine prescriptions with injuries among US military service members.

ABSTRACT: Given the high rates of physical trauma and pain among service members, opioid-prescribing practices and use patterns have significant implications for the well-being of service members and can affect military medicine and personnel readiness. This study measured the association between prescribed opioid and benzodiazepine medications and subsequently reported injuries (accidental, alcohol and drug related, self-inflicted, and violence related) among active duty military members. Participants were service members who entered the military between January 1, 2005, and June 30, 2010. In a nested case-control design, we compared individuals with injuries to individuals without injuries with respect to their opioid and benzodiazepine prescriptions in the 30 days before the injury of an index case. We used a multiintercept, logistic regression model to compare coefficient estimates by injury type. Overall, approximately 17% of individuals with an injury and 4% of individuals without an injury had a recorded opioid prescription. Individuals with an injury of any type had greater odds of prior exposure to opioid prescriptions than controls. Although a dose-response effect was observed for all injury types, it reached a plateau sooner for natural or environmental accidents and self-inflicted injuries relative to alcohol-related and drug-related injuries, violence-related injuries, vehicle accidents, accidental falls, and other accidents. Benzodiazepine prescriptions were found in 3.5% of individuals with an injury and 0.5% of individuals without an injury. The association between benzodiazepine prescriptions and injuries was strongest for natural and environmental accidents.

Impact of lesion morphology on stent elongation during bifurcation PCI: an in vivo OCT study.

BACKGROUND: Recent observations in silico and in vivo reported that, during proximal optimisation technique, drug-eluting stents (DES) elongate, challenging conventional wisdom. The interaction between plaque morphology and radial expansion is well established, but little is known about the impact of plaque morphology on elongation. AIMS: We aimed to assess the longitudinal mechanical behaviour of contemporary DES in vivo and evaluate the relationship between post-percutaneous coronary intervention (PCI) stent elongation and lesion morphology, as assessed with optical coherence tomography (OCT). METHODS: Patients treated with OCT-guided PCI to left main or left anterior descending artery bifurcations, between July 2017 and March 2022, from the King's Optical coherence Database Analysis Compendium were included. Patients were excluded if there were overlapping stents, if they had undergone prior PCI, or if there was inadequate image quality. Lesions were characterised as fibrocalcific, fibrous or lipid-rich by pre-PCI OCT. Following stent post-dilatation, stent expansion and final stent length were assessed. The primary outcome was the percentage change in stent length from baseline. RESULTS: Of 501 eligible consecutive patients from this period, 116 were included. The median age was 66 years (interquartile range [IQR] 57-76), 31% were female, and 53.4% were treated for an acute coronary syndrome. A total of 50.0% of lesions were classified as fibrocalcific, 6.9% were fibrous, and 43.1% were lipid-rich. The change in relative stent length was 4.4% (IQR 1.0-8.9), with an increase of 3.1% (IQR 0.5-6.3) in fibrocalcific lesions, 3.3% (IQR 0.5-5.9) in fibrous lesions, and 6.4% (IQR 3.1-11.1) in lipid-rich plaque (p=0.006). In multivariate regression modelling, lipid-rich plaque was an independent predictor of stent elongation (odds ratio 3.689, 95% confidence interval: 1.604-8.484). CONCLUSIONS: Contemporary DES elongate following implantation and post-dilatation, and this is significantly mediated by plaque morphology. This is an important consideration when planning a strategy for DES implantation.

Differentiating Left Ventricular Remodeling in Aortic Stenosis From Systemic Hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy occurs in both aortic stenosis (AS) and systemic hypertension (HTN) in response to wall stress. However, differentiation of hypertrophy due to these 2 etiologies is lacking. The aim was to study the 3-dimensional geometric remodeling pattern in severe AS pre- and postsurgical aortic valve replacement and to compare with HTN and healthy controls. METHODS: Ninety-one subjects (36 severe AS, 19 HTN, and 36 healthy controls) underwent cine cardiac magnetic resonance. Cardiac magnetic resonance was repeated 8 months post-aortic valve replacement (n=18). Principal component analysis was performed on the 3-dimensional meshes reconstructed from 109 cardiac magnetic resonance scans of 91 subjects at end-diastole. Principal component analysis modes were compared across experimental groups together with conventional metrics of shape, strain, and scar. RESULTS: A unique AS signature was identified by wall thickness linked to a LV left-right axis shift and a decrease in short-axis eccentricity. HTN was uniquely linked to increased septal thickness. Combining these 3 features had good discriminative ability between AS and HTN (area under the curve, 0.792). The LV left-right axis shift was not reversible post-aortic valve replacement, did not associate with strain, age, or sex, and was predictive of postoperative LV mass regression (R2=0.339, P=0.014). CONCLUSIONS: Unique remodeling signatures might differentiate the etiology of LV hypertrophy. Preliminary findings suggest that LV axis shift is characteristic in AS, is not reversible post-aortic valve replacement, predicts mass regression, and may be interpreted to be an adaptive mechanism.

Validation of the CREST model and comparison with SCAI shock classification for the prediction of circulatory death in resuscitated out-of-hospital cardiac arrest.

AIMS: We validated the CREST model, a 5 variable score for stratifying the risk of circulatory aetiology death (CED) following out-of-hospital cardiac arrest (OHCA) and compared its discrimination with the SCAI shock classification. Circulatory aetiology death occurs in approximately a third of patients admitted after resuscitated OHCA. There is an urgent need for improved stratification of the patient with OHCA on arrival to a cardiac arrest centre to improve patient selection for invasive interventions. METHODS AND RESULTS: The CREST model and SCAI shock classification were applied to a dual-centre registry of 723 patients with cardiac aetiology OHCA, both with and without ST-elevation myocardial infarction (STEMI), between May 2012 and December 2020. The primary endpoint was a 30-day CED. Of 509 patients included (62.3 years, 75.4% male), 125 patients had CREST = 0 (24.5%), 162 had CREST = 1 (31.8%), 140 had CREST = 2 (27.5%), 75 had CREST = 3 (14.7%), 7 had a CREST of 4 (1.4%), and no patients had CREST = 5. Circulatory aetiology death was observed in 91 (17.9%) patients at 30 days [STEMI: 51/289 (17.6%); non-STEMI (NSTEMI): 40/220 (18.2%)]. For the total population, and both NSTEMI and STEMI subpopulations, an increasing CREST score was associated with increasing CED (all P < 0.001). The CREST score and SCAI classification had similar discrimination for the total population [area under the receiver operating curve (AUC) = 0.72/calibration slope = 0.95], NSTEMI cohort (AUC = 0.75/calibration slope = 0.940), and STEMI cohort (AUC = 0.69 and calibration slope = 0.925). Area under the receiver operating curve meta-analyses demonstrated no significant differences between the two classifications. CONCLUSION: The CREST model and SCAI shock classification show similar prediction results for the development of CED after OHCA.

Race- and Ethnicity-Related Differences in Heart Failure With Preserved Ejection Fraction Using Natural Language Processing.

Background: Heart failure with preserved ejection fraction (HFpEF) is the predominant form of HF in older adults. It represents a heterogenous clinical syndrome that is less well understood across different ethnicities. Objectives: This study aimed to compare the clinical presentation and assess the diagnostic performance of existing HFpEF diagnostic tools between ethnic groups. Methods: A validated Natural Language Processing (NLP) algorithm was applied to the electronic health records of a large London hospital to identify patients meeting the European Society of Cardiology criteria for a diagnosis of HFpEF. NLP extracted patient demographics (including self-reported ethnicity and socioeconomic status), comorbidities, investigation results (N-terminal pro-B-type natriuretic peptide, H2FPEF scores, and echocardiogram reports), and mortality. Analyses were stratified by ethnicity and adjusted for socioeconomic status. Results: Our cohort consisted of 1,261 (64%) White, 578 (29%) Black, and 134 (7%) Asian patients meeting the European Society of Cardiology HFpEF diagnostic criteria. Compared to White patients, Black patients were younger at diagnosis and more likely to have metabolic comorbidities (obesity, diabetes, and hypertension) but less likely to have atrial fibrillation (30% vs 13%; P < 0.001). Black patients had lower N-terminal pro-B-type natriuretic peptide levels and a lower frequency of H2FPEF scores ≥6, indicative of likely HFpEF (26% vs 44%; P < 0.0001). Conclusions: Leveraging an NLP-based artificial intelligence approach to quantify health inequities in HFpEF diagnosis, we discovered that established markers systematically underdiagnose HFpEF in Black patients, possibly due to differences in the underlying comorbidity patterns. Clinicians should be aware of these limitations and its implications for treatment and trial recruitment.