Artificial intelligence methods for improved detection of undiagnosed heart failure with preserved ejection fraction.

AIM: Heart failure with preserved ejection fraction (HFpEF) remains under-diagnosed in clinical practice despite accounting for nearly half of all heart failure (HF) cases. Accurate and timely diagnosis of HFpEF is crucial for proper patient management and treatment. In this study, we explored the potential of natural language processing (NLP) to improve the detection and diagnosis of HFpEF according to the European Society of Cardiology (ESC) diagnostic criteria. METHODS AND RESULTS: In a retrospective cohort study, we used an NLP pipeline applied to the electronic health record (EHR) to identify patients with a clinical diagnosis of HF between 2010 and 2022. We collected demographic, clinical, echocardiographic and outcome data from the EHR. Patients were categorized according to the left ventricular ejection fraction (LVEF). Those with LVEF ≥50% were further categorized based on whether they had a clinician-assigned diagnosis of HFpEF and if not, whether they met the ESC diagnostic criteria. Results were validated in a second, independent centre. We identified 8606 patients with HF. Of 3727 consecutive patients with HF and LVEF ≥50% on echocardiogram, only 8.3% had a clinician-assigned diagnosis of HFpEF, while 75.4% met ESC criteria but did not have a formal diagnosis of HFpEF. Patients with confirmed HFpEF were hospitalized more frequently; however the ESC criteria group had a higher 5-year mortality, despite being less comorbid and experiencing fewer acute cardiovascular events. CONCLUSIONS: This study demonstrates that patients with undiagnosed HFpEF are an at-risk group with high mortality. It is possible to use NLP methods to identify likely HFpEF patients from EHR data who would likely then benefit from expert clinical review and complement the use of diagnostic algorithms.

MIRACLE2 Score Compared With Downtime and Current Selection Criterion for Invasive Cardiovascular Therapies After OHCA.

BACKGROUND: The MIRACLE2 score is the only risk score that does not incorporate and can be used for selection of therapies after out-of-hospital cardiac arrest (OHCA). OBJECTIVES: This study sought to compare the discrimination performance of the MIRACLE2 score, downtime, and current randomized controlled trial (RCT) recruitment criteria in predicting poor neurologic outcome after out-of-hospital cardiac arrest (OHCA). METHODS: We used the EUCAR (European Cardiac Arrest Registry), a retrospective cohort from 6 centers (May 2012-September 2022). The primary outcome was poor neurologic outcome on hospital discharge (cerebral performance category 3-5). RESULTS: A total of 1,259 patients (total downtime = 25 minutes; IQR: 15-36 minutes) were included in the study. Poor outcome occurred in 41.8% with downtime <30 minutes and in 79.3% for those with downtime >30 minutes. In a multivariable logistic regression analysis, MIRACLE2 had a stronger association with outcome (OR: 2.23; 95% CI: 1.98-2.51; P < 0.0001) than zero flow (OR: 1.07; 95% CI: 1.01-1.13; P = 0.013), low flow (OR: 1.04; 95% CI: 0.99-1.09; P = 0.054), and total downtime (OR: 0.99; 95% CI: 0.95-1.03; P = 0.52). MIRACLE2 had substantially superior discrimination for the primary endpoint (AUC: 0.877; 95% CI: 0.854-0.897) than zero flow (AUC: 0.610; 95% CI: 0.577-0.642), low flow (AUC: 0.725; 95% CI: 0.695-0.754), and total downtime (AUC: 0.732; 95% CI: 0.701-0.760). For those modeled for exclusion from study recruitment, the positive predictive value of MIRACLE2 ≥5 for poor outcome was significantly higher (0.92) than the CULPRIT-SHOCK (Culprit lesion only PCI Versus Multivessel PCI in Cardiogenic Shock) (0.80), EUROSHOCK (Testing the value of Novel Strategy and Its Cost Efficacy In Order to Improve the Poor Outcomes in Cardiogenic Shock) (0.74) and ECLS-SHOCK (Extra-corporeal life support in Cardiogenic shock) criteria (0.81) (P < 0.001). CONCLUSIONS: The MIRACLE2 score has superior prediction of outcome after OHCA than downtime and higher discrimination of poor outcome than the current RCT recruitment criteria. The potential for the MIRACLE2 score to improve the selection of OHCA patients should be evaluated formally in future RCTs.

Coronary Artery Disease in Patients with Severe Mental Illness.

Severe mental illnesses (SMI), such as schizophrenia and bipolar disorder, are associated with a decrease in life expectancy of up to two decades compared with the general population, with cardiovascular disease as the leading cause of death. SMI is associated with increased cardiovascular risk profile and early onset of incident cardiovascular disease. Following an acute coronary syndrome, patients with SMI have a worse prognosis, but are less likely to receive invasive treatment. In this narrative review, the management of coronary artery disease in patients with SMI is discussed, and avenues for future research are highlighted.

The effect of ethnicity and socioeconomic status on outcomes after resuscitated out-of-hospital cardiac arrest - Findings from a tertiary centre in South London.

Background: Out-of-hospital cardiac arrest is a common cause of morbidity and mortality, and ethnic variation in outcomes is recognised. We investigated ethnic and socioeconomic differences in arrest circumstances, rates of coronary artery disease, treatment, and outcomes in resuscitated OOHCA. Methods: Patients with resuscitated OOHCA of suspected cardiac aetiology were included in the King's Out-of-Hospital Cardiac Arrest Registry between 1-May-2012 and 31-December-2020. Results: Of 526 patients (median age 62.0 years, IQR 21.1, 74.1% male), 414 patients (78.7%) were White, 35 (6.7%) were Asian, and 77 (14.6%) were Black. Black patients had more co-existent hypertension (p = 0.007) and cardiomyopathy (p = 0.003), but less prior coronary revascularisation (p = 0.026) compared with White/Asian patients. There were no ethnic differences in location, witnesses, or bystander CPR, but Black patients had more non-shockable rhythms (p < 0.001). Black patients received less immediate coronary angiography (p < 0.001) and percutaneous coronary intervention (p < 0.001) but had lower rates of CAD (p = 0.004) than White/Asian patients. All-cause mortality at 12 months was highest amongst Black patients, followed by Asian and then White patients (57.1% vs 48.6% vs 41.3%, p = 0.032). In Black patients, excess mortality was driven by higher rates of multi-organ dysfunction but lower cardiac death than White/Asian patients, with cardiac death highest amongst Asian patients (p = 0.009). Socioeconomic status had no effect on mortality, and in a multivariable logistic regression, age, location, witnesses, and Black compared to White ethnicity were independent predictors of mortality, whilst social deprivation was not. Conclusion: In this single-centre study, Black patients had higher mortality after resuscitated OOHCA than White/Asian patients. This may be in part due to differing underlying aetiology rather than differences in arrest circumstances or social deprivation.

Intravascular lithotripsy in the treatment of coronary artery calcification in a high-risk real world population.

BACKGROUND: The DISRUPT-CAD study series demonstrated feasibility and safety of intravascular lithotripsy (IVL) in selected patients, but applicability across a broad range of clinical scenarios remains unclear. AIMS: This study aims to evaluate the procedural and clinical outcomes of IVL in a high-risk real-world cohort, compared to a regulatory approval cohort. METHODS: Consecutive patients treated with IVL and percutaneous coronary intervention at our center from May 2016 to April 2020 were included. Comparison was made between those enrolled in the DISRUPT-CAD series of studies to those with calcified lesions but an exclusion criteria. RESULTS: Among 177 patients treated with IVL, 142 were excluded from regulatory trials due to acute coronary syndrome presentation (47.2%), left ventricular ejection fraction <40% (22.5%), chronic renal failure (12.0%), or use of mechanical circulatory support (8.5%). This clinical cohort had a higher SYNTAX score (22.6 ± 12.1 vs. 17.4 ± 9.9, p = 0.019), and more treated ACC/AHA C lesions (56.3% vs. 37.1%, p = 0.042). Rates of device success (93.7% vs. 100.0%, p = 0.208), procedural success (96.5% vs. 100.0%, p = 0.585), and minimal lumen area gain (221.2 ± 93.7% vs. 198.6 ± 152.0%, p = 0.807) were similar in both groups. The DISRUPT-CAD cohort had no in-hospital mortality, 30-day major adverse cardiac events (MACE), or 30-day target vessel revascularization (TVR). The clinical cohort had an in-hospital mortality of 4.2%, 30-day MACE of 7.8%, and 30-day TVR of 1.5%. There was no difference in 12-month TVR (2.9% vs. 2.2%; p = 0.825). Twelve-month MACE was higher in the clinical cohort (21.1% vs. 8.6%, p = 0.03). CONCLUSION: IVL use remains associated with high clinical efficacy, procedural success, and low complication rates in a real-world population previously excluded from regulatory approving trials.

Coronary Wave Intensity Analysis as an Invasive and Vessel-Specific Index of Myocardial Viability.

BACKGROUND: Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium-enhanced cardiac magnetic resonance imaging. METHODS: Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery. RESULTS: Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (-5240±3772 versus -1873±1605 W m-2 s-1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability (area under the curve 0.812 versus 0.757, P=0.649); a threshold of -2500 W m-2 s-1 had 86% sensitivity and 76% specificity. CONCLUSIONS: Backward compression wave energy has accuracy similar to that of late-gadolinium-enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina.

MIRACLE2 Score and SCAI Grade to Identify Patients With Out-of-Hospital Cardiac Arrest for Immediate Coronary Angiography.

OBJECTIVES: The purpose of this study was to evaluate the impact of performing immediate coronary angiography (CAG) after out-of-hospital cardiac arrest (OHCA) with stratification of predicted neurologic injury and cardiogenic shock on arrival to a center. BACKGROUND: The role of immediate CAG for patients with OHCA is unclear, which may in part be explained by the majority of patients dying of hypoxic brain injury. METHODS: Between May 2012 and July 2020, patients from 5 European centers were included in the EUCAR (European Cardiac Arrest Registry). Patients were retrospectively classified into low vs high neurologic risk (MIRACLE2 score 0-3 vs ≥4) and degree of cardiogenic shock on arrival (Society for Cardiovascular Angiography and Interventions [SCAI] grade A vs B-E). A multivariable logistic regression analysis including immediate CAG was performed for the primary outcome of survival with good neurologic outcome (Cerebral Performance Category 1 or 2) at hospital discharge. RESULTS: Nine hundred twenty-six patients were included in the registry, with 405 (43.7%) in the low-risk group and 521 (56.3%) in the high-risk group. Immediate CAG was independently associated with improved survival with good neurologic outcome in the low MIRACLE2 risk group with ST-segment elevation myocardial infarction (OR: 11.80; 95% CI: 2.24-76.74; P = 0.048) and with SCAI grade B to E shock (OR: 3.23; 95% CI: 1.10-9.50; P = 0.031). No subgroups, including those with ST-segment elevation myocardial infarction and with SCAI grade B to E shock, achieved any benefit from early CAG in the high MIRACLE2 group. CONCLUSIONS: Combined classification of patients with OHCA with 12-lead electrocardiography, MIRACLE2 score 0 to 3, and SCAI grade B to E identifies a potential cohort of patients at low risk for neurologic injury who benefit most from immediate CAG.

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction (NIHR Health Informatics Collaborative: TROP-CABG study).

Implications of elevated troponin on time-to-surgery in non-ST elevation myocardial infarction(NIHR Health Informatics Collaborative:TROP-CABG study). Benedetto et al. BACKGROUND: The optimal timing of coronary artery bypass grafting (CABG) in patients with non-ST elevation myocardial infarction (NSTEMI) and the utility of pre-operative troponin levels in decision-making remains unclear. We investigated (a) the association between peak pre-operative troponin and survival post-CABG in a large cohort of NSTEMI patients and (b) the interaction between troponin and time-to-surgery. METHODS AND RESULTS: Our cohort consisted of 1746 patients (1684 NSTEMI; 62 unstable angina) (mean age 69 ± 11 years,21% female) with recorded troponins that had CABG at five United Kingdom centers between 2010 and 2017. Time-segmented Cox regression was used to investigate the interaction of peak troponin and time-to-surgery on early (within 30 days) and late (beyond 30 days) survival. Average interval from peak troponin to surgery was 9 ± 15 days, with 1466 (84.0%) patients having CABG during the same admission. Sixty patients died within 30-days and another 211 died after a mean follow-up of 4 ± 2 years (30-day survival 0.97 ± 0.004 and 5-year survival 0.83 ± 0.01). Peak troponin was a strong predictor of early survival (adjusted P = 0.002) with a significant interaction with time-to-surgery (P interaction = 0.007). For peak troponin levels <100 times the upper limit of normal, there was no improvement in early survival with longer time-to-surgery. However, in patients with higher troponins, early survival increased progressively with a longer time-to-surgery, till day 10. Peak troponin did not influence survival beyond 30 days (adjusted P = 0.64). CONCLUSIONS: Peak troponin in NSTEMI patients undergoing CABG was a significant predictor of early mortality, strongly influenced the time-to-surgery and may prove to be a clinically useful biomarker in the management of these patients.

Prognostic Significance of Ventricular Arrhythmias in 13 444 Patients With Acute Coronary Syndrome: A Retrospective Cohort Study Based on Routine Clinical Data (NIHR Health Informatics Collaborative VA-ACS Study).

Background A minority of acute coronary syndrome (ACS) cases are associated with ventricular arrhythmias (VA) and/or cardiac arrest (CA). We investigated the effect of VA/CA at the time of ACS on long-term outcomes. Methods and Results We analyzed routine clinical data from 5 National Health Service trusts in the United Kingdom, collected between 2010 and 2017 by the National Institute for Health Research Health Informatics Collaborative. A total of 13 444 patients with ACS, 376 (2.8%) of whom had concurrent VA, survived to hospital discharge and were followed up for a median of 3.42 years. Patients with VA or CA at index presentation had significantly increased risks of subsequent VA during follow-up (VA group: adjusted hazard ratio [HR], 4.15 [95% CI, 2.42-7.09]; CA group: adjusted HR, 2.60 [95% CI, 1.23-5.48]). Patients who suffered a CA in the context of ACS and survived to discharge also had a 36% increase in long-term mortality (adjusted HR, 1.36 [95% CI, 1.04-1.78]), although the concurrent diagnosis of VA alone during ACS did not affect all-cause mortality (adjusted HR, 1.03 [95% CI, 0.80-1.33]). Conclusions Patients who develop VA or CA during ACS who survive to discharge have increased risks of subsequent VA, whereas those who have CA during ACS also have an increase in long-term mortality. These individuals may represent a subgroup at greater risk of subsequent arrhythmic events as a result of intrinsically lower thresholds for developing VA.

Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study.

BACKGROUND: There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. METHODS AND FINDINGS: We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. CONCLUSIONS: These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. TRIAL REGISTRATION: ClinicalTrials.gov - NCT03507309.

Clinical Significance of Early Echocardiographic Changes after Resuscitated Out-of-Hospital Cardiac Arrest.

BACKGROUND: Left Ventricular Systolic Dysfunction (LVSD) is common after out-of-hospital cardiac arrest (OOHCA) and can manifest globally or regionally, although its clinical significance has not been robustly studied. This study evaluates the association between LVSD, extent of coronary artery disease (CAD) and outcome in those undergoing early echocardiography and coronary angiography after OOHCA. METHODS: Trans-thoracic echocardiography (TTE) was performed in OOHCA patients on arrival to our centre between May 2012 and December 2017. Rates of cardiogenic shock and extent of CAD, respectively classified by SCAI grade and the SYNTAX score, were measured. The primary end-point was 12-month mortality. RESULTS: From 398 patients in the King's Out of Hospital Cardiac Arrest Registry (KOCAR), 266 patients (median age 61 [53-71], 76% male) underwent both TTE and coronary angiography on arrival. 96 patients (36%) had significant LVSD (Left Ventricular Ejection Fraction [LVEF] <40%) and 139 (52.2%) patients had regional wall motion abnormalities (RWMAs). Patients with LVEF <40% had more SCAI grade C-E shock (65.3% vs. 34.5%, p <0.001) and higher 12-month mortality (55.2% vs 31.8%, p <0.001) which was more likely to be due to a cardiac aetiology (27.3% vs 5.3%, p <0.001). Patients with RWMAs had higher median SYNTAX scores (14.75 vs 7, p=0.001), culprit coronary lesions (83.5% vs. 45.3%, p <0.001) and lower 12-month mortality (29.5% vs 52%, p <0.001). CONCLUSIONS: Patients with LVEF <40% at presentation have an increased mortality, driven by cardiac aetiology death, while the presence of RWMAs is associated with a higher rate of culprit coronary lesions, representing a potentially reversible cause of the arrest, and improved survival at 1 year.

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.

SCAI cardiogenic shock classification after out of hospital cardiac arrest and association with outcome.

OBJECTIVES: We aimed to validate the Society for Cardiovascular Angiography and Interventions (SCAI) classification to evaluate association with outcome in a real-world population and effect of invasive therapies. BACKGROUND: Cardiogenic shock is common after Out of Hospital Cardiac Arrest (OOHCA) but is often multifactorial and challenging to stratify. METHODS: The SCAI shock grade was applied to an observational registry of OOHCA patients on admission to our center between 2012 and 2017. The primary end-point was 30-day mortality and secondary end-points were mode of death and 12-month mortality. Provision of early CAG and mechanical circulatory support (MCS) was evaluated by SCAI shock grade using logistic regression. RESULTS: Three hundred and ninety-three patients (median age 64.3 years (24.9% females) were included. One hundred and seven patients (27.2%) were in Grade A, 94 (23.9%) in Grade B, 66 (16.8%) in Grade C, 91 (23.2%) in Grade D, and 35 (8.9%) in Grade E. There was a step-wise significant increase in 30-day mortality with increasing shock grade (A 28.9% vs. B 33.0% vs. C 54.5% vs. D 59.3% vs. E 82.9%; p < .0001). With worsening shock grade, requirement for renal replacement therapy and mortality from multiorgan dysfunction syndrome and cardiogenic causes increased. Early CAG was performed equally in all groups but was significantly associated with reduced mortality in SCAI grade D only (OR 0.26 [CI 0.08-0.91], p = .036). CONCLUSIONS: Increasing SCAI shock grade after OOHCA is associated with 30-day mortality, requirement for renal replacement therapy and mortality attributed to multiorgan dysfunction syndrome and cardiac etiology death.

Invasive versus non-invasive management of older patients with non-ST elevation myocardial infarction (SENIOR-NSTEMI): a cohort study based on routine clinical data.

BACKGROUND: Previous trials suggest lower long-term risk of mortality after invasive rather than non-invasive management of patients with non-ST elevation myocardial infarction (NSTEMI), but the trials excluded very elderly patients. We aimed to estimate the effect of invasive versus non-invasive management within 3 days of peak troponin concentration on the survival of patients aged 80 years or older with NSTEMI. METHODS: Routine clinical data for this study were obtained from five collaborating hospitals hosting NIHR Biomedical Research Centres in the UK (all tertiary centres with emergency departments). Eligible patients were 80 years old or older when they underwent troponin measurements and were diagnosed with NSTEMI between 2010 (2008 for University College Hospital) and 2017. Propensity scores (patients' estimated probability of receiving invasive management) based on pretreatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days of peak troponin concentration without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and compared the rate of hospital admissions for heart failure. FINDINGS: Of the 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin concentration and 375 were excluded because of extreme propensity scores. The remaining 1500 patients had a median age of 86 (IQR 82-89) years of whom (845 [56%] received non-invasive management. During median follow-up of 3·0 (IQR 1·2-4·8) years, 613 (41%) patients died. The adjusted cumulative 5-year mortality was 36% in the invasive management group and 55% in the non-invasive management group (adjusted hazard ratio 0·68, 95% CI 0·55-0·84). Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0·67, 95% CI 0·48-0·93). INTERPRETATION: The survival advantage of invasive compared with non-invasive management appears to extend to patients with NSTEMI who are aged 80 years or older. FUNDING: NIHR Imperial Biomedical Research Centre, as part of the NIHR Health Informatics Collaborative.

Prognostic significance of troponin level in 3121 patients presenting with atrial fibrillation (The NIHR Health Informatics Collaborative TROP-AF study).

Background Patients presenting with atrial fibrillation (AF) often undergo a blood test to measure troponin, but interpretation of the result is impeded by uncertainty about its clinical importance. We investigated the relationship between troponin level, coronary angiography, and all-cause mortality in real-world patients presenting with AF. Methods and Results We used National Institute of Health Research Health Informatics Collaborative data to identify patients admitted between 2010 and 2017 at 5 tertiary centers in the United Kingdom with a primary diagnosis of AF. Peak troponin results were scaled as multiples of the upper limit of normal. A total of 3121 patients were included in the analysis. Over a median follow-up of 1462 (interquartile range, 929-1975) days, there were 586 deaths (18.8%). The adjusted hazard ratio for mortality associated with a positive troponin (value above upper limit of normal) was 1.20 (95% CI, 1.01-1.43; P<0.05). Higher troponin levels were associated with higher risk of mortality, reaching a maximum hazard ratio of 2.6 (95% CI, 1.9-3.4) at ≈250 multiples of the upper limit of normal. There was an exponential relationship between higher troponin levels and increased odds of coronary angiography. The mortality risk was 36% lower in patients undergoing coronary angiography than in those who did not (adjusted hazard ratio, 0.61; 95% CI, 0.42-0.89; P=0.01). Conclusions Increased troponin was associated with increased risk of mortality in patients presenting with AF. The lower hazard ratio in patients undergoing invasive management raises the possibility that the clinical importance of troponin release in AF may be mediated by coronary artery disease, which may be responsive to revascularization.

Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres.

OBJECTIVE: To determine the relation between age and troponin level and its prognostic implication. DESIGN: Retrospective cohort study. SETTING: Five cardiovascular centres in the UK National Institute for Health Research Health Informatics Collaborative (UK-NIHR HIC). PARTICIPANTS: 257 948 consecutive patients undergoing troponin testing for any clinical reason between 2010 and 2017. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: 257 948 patients had troponin measured during the study period. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured during the patient's hospital stay. Troponin levels were standardised as a multiple of each laboratory's 99th centile of the upper limit of normal (ULN). During a median follow-up of 1198 days (interquartile range 514-1866 days), 55 850 (21.7%) deaths occurred. A positive troponin result (that is, higher than the upper limit of normal) signified a 3.2 higher mortality hazard (95% confidence interval 3.1 to 3.2) over three years. Mortality varied noticeably with age, with a hazard ratio of 10.6 (8.5 to 13.3) in 18-29 year olds and 1.5 (1.4 to 1.6) in those older than 90. A positive troponin result was associated with an approximately 15 percentage points higher absolute three year mortality across all age groups. The excess mortality with a positive troponin result was heavily concentrated in the first few weeks. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. A direct relation was seen between troponin level and mortality in patients without acute coronary syndrome (ACS, n=120 049), whereas an inverted U shaped relation was found in patients with ACS (n=14 468), with a paradoxical decline in mortality at peak troponin levels >70×ULN. In the group with ACS, the inverted U shaped relation persisted after multivariable adjustment in those who were managed invasively; however, a direct positive relation was found between troponin level and mortality in patients managed non-invasively. CONCLUSIONS: A positive troponin result was associated with a clinically important increased mortality, regardless of age, even if the level was only slightly above normal. The excess mortality with a raised troponin was heavily concentrated in the first few weeks. STUDY REGISTRATION: ClinicalTrials.gov NCT03507309.

Long-term outcomes in surgically ineligible patients managed with percutaneous coronary revascularization or medical therapy.

The objective of the study was to report clinical outcomes of patients unsuitable for surgical coronary revascularization (CABG) treated with percutaneous revascularization (PCI) or medical therapy alone (MT). The decision to revascularize patients referred for CABG but who are unsuitable should be made at Heart Team meetings. The clinical outcomes in this important patient subset are not known, and while cases are considered individually, these decisions are not guided by robust data. Clinical data were analyzed for patients referred to the Heart Team for consideration of CABG over a 4-year period in a UK tertiary referral center. Outcome data for those managed with urgent PCI or MT were considered over a further 3-year period. 133 patients were treated with PCI and 117 with MT. MACE at 30 days were no different between groups (MT 10.3% versus PCI 12.2%); however, at 1 year MACE were higher in the MT group (MT 39.3% versus PCI 26.7%, P < 0.01). Log rank for MACE-free survival to 1 and 3 years was significantly lower in the MT group [HR 1.77 (0.60-1.11); P < 0.001]. Residual SYNTAX was an independent predictor of death. MT [OR 1.75 (1.03-2.99); P = 0.04] and a residual SYNTAX score [OR 6.45 (2.53-16.45); P < 0.001] were independent predictors of MACE at 1 year in the whole group. Our data reveal better outcomes in patients treated with PCI over MT at 1-3 years in CABG-ineligible patients. Patients without complete revascularization have worse outcomes.

Occlutech percutaneous patent foramen ovale closure: Safety and efficacy registry (OPPOSE).

INTRODUCTION: Safety and efficacy data on patent foramen ovale (PFO) closure with the Occlutech Figulla Flex II device are lacking. We undertook a fully monitored prospective Registry on PFO closure using this device. METHODS: 100 patients undergoing PFO closure were enrolled into the OPPOSE Registry at 6 UK centres. The primary endpoint was PFO closure (grade 0 or 1 shunt) at 6-month BCTTE assessed by Corelab. Secondary endpoints included implantation success, complications, and atrial fibrillation during follow-up. RESULTS: 100 patients aged 43.8±11.5years, 53% male, were recruited. Indications for PFO closure included stroke (56%), TIA (29%) systemic embolism (4%) and MI (3%). Closure was undertaken under GA (44%) or LA (56%), with TOE (45%), ICE (31%), no imaging (20%) or TTE (3%). Balloon sizing was used in 98% of cases and showed a tunnel length of 7.3±3.6mm, primum-secundum separation of 7.0±2.9mm and basal inlet width of 8.5±3.5mm. Implantation was successful in all cases using 18mm (9%), 25mm (80%), 30mm (10%) and 35mm (1%) devices. 5 patients were lost to follow-up. 92 patients underwent six-month BCTTE. The primary endpoint of PFO closure (grade 0 or 1 shunt) at six months was 79.3%. One patient developed major bleeding (BARC 3b), one patient required vascular surgery, and in one patient device embolization was noted at six months and a larger device implanted. There was one case of new atrial fibrillation. CONCLUSIONS: This first prospective monitored data for the Occlutech Figulla Flex II device demonstrates good safety and efficacy data at implant and six-month follow-up.

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/.