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.

Oral Class I and III antiarrhythmic drugs for maintaining sinus rhythm after catheter ablation of atrial fibrillation.

BACKGROUND: Recurrence of atrial tachyarrhythmias (ATa) following catheter ablation for atrial fibrillation (AF) is a common problem. Antiarrhythmic drugs have been used shortly after ablation in an attempt to maintain sinus rhythm, particularly Class I and III agents. However, it still needs to be established if the use of Class I or III antiarrhythmic medications, or both, reduce the risk of recurrence of ATa. OBJECTIVES: To assess the effects of oral Class I and III antiarrhythmic drugs versus control (standard medical therapy without Class I or III antiarrhythmics, or placebo) for maintaining sinus rhythm in people undergoing catheter ablation for AF. SEARCH METHODS: We systematically searched CENTRAL, MEDLINE, Embase, Web of Science Core Collection, and two clinical trial registers without restrictions on language or date to 5 August 2022. SELECTION CRITERIA: We sought published, unpublished, and ongoing parallel-design, randomised controlled trials (RCTs) involving adult participants undergoing ablation for AF, with subsequent comparison of Class I and/or III antiarrhythmic use versus control (standard medical therapy or non-Class I and/or III antiarrhythmic use). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and performed meta-analyses with risk ratios (RR) and Peto odds ratios (Peto OR). Our primary outcomes were recurrence of atrial tachyarrhythmias; adverse events: thromboembolic events; adverse events: myocardial infarction; adverse events: new diagnosis of heart failure; and adverse events: requirement for one or more hospitalisations for atrial tachyarrhythmia. Our secondary outcomes were: all-cause mortality; and requirement for one or more repeat ablations. Where possible, we performed comparison analysis by Class I and/or III antiarrhythmic and divided follow-up periods for our primary outcome. We performed comprehensive assessments of risk of bias and certainty of evidence applying the GRADE methodology. MAIN RESULTS: We included nine RCTs involving a total of 3269 participants. Participants were on average 59.3 years old; 71.0% were male; and 72.9% and 27.4% had paroxysmal and persistent AF, respectively. Class I and/or III antiarrhythmics may reduce recurrence of ATa at 0 to 3 months postablation (risk ratio (RR) 0.74, 95% confidence interval (CI) 0.59 to 0.94, 8 trials, 3046 participants, low-certainty evidence) and likely reduce recurrence at > 3 to 6 months, our a priori primary time point (RR 0.85, 95% CI 0.78 to 0.93, 5 trials, 2591 participants, moderate-certainty evidence). Beyond six months the evidence is very uncertain, and the benefit of antiarrhythmics may not persist (RR 1.14, 95% CI 0.84 to 1.55, 4 trials, 2244 participants, very low-certainty evidence). The evidence suggests that Class I and/or III antiarrhythmics may not increase the risk of thromboembolic events, myocardial infarction, all-cause mortality, or requirement for repeat ablation, at 0 to 3, > 3 to 6, and > 6 months (where data were available; low- to very low-certainty evidence). The use of Class I and/or III antiarrhythmics postablation likely reduces hospitalisations for ATa by approximately 57% at 0 to 3 months (RR 0.43, 95% CI 0.28 to 0.64, moderate-certainty evidence). No data were available beyond three months. No data were available on new diagnoses of heart failure. Fewer data were available for Class I and III antiarrhythmics individually. Based on only one and two trials (n = 125 to 309), Class I antiarrhythmics may have little effect on recurrence of ATa at 0 to 3, > 3 to 6, and > 6 months (RR 0.88, 95% CI 0.64 to 1.20, 2 trials, 309 participants; RR 0.54, 95% CI 0.25 to 1.19, 1 trial, 125 participants; RR 0.87, 95% CI 0.57 to 1.32, 1 trial, 125 participants; low-certainty evidence throughout); requirement for hospitalisation for ATa at 0 to 3 months (low-certainty evidence); or requirement for repeat ablation at 0 to 3 months (low-certainty evidence). No data were available for thromboembolic events, myocardial infarction, new diagnosis of heart failure, or all-cause mortality at any time points, or hospitalisation or repeat ablation beyond three months. Class III antiarrhythmics may have little effect on recurrence of ATa at up to 3 months and at > 3 to 6 months (RR 0.76, 95% CI 0.50 to 1.16, 4 trials, 599 participants, low-certainty evidence; RR 0.82, 95% CI 0.62 to 1.09, 2 trials, 318 participants, low-certainty evidence), and beyond 6 months one trial reported a possible increase in recurrence of ATa (RR 1.95, 95% CI 1.29 to 2.94, 1 trial, 112 participants, low-certainty evidence). Class III antiarrhythmics likely reduce hospitalisations for ATa at 0 to 3 months (RR 0.40, 95% CI 0.26 to 0.63, moderate-certainty evidence), and may have little effect on all-cause mortality (low- to very low-certainty evidence). The effect of Class III antiarrhythmics on thromboembolic events and requirement for repeat ablation was uncertain (very low-certainty evidence for both outcomes). No data were available for myocardial infarction or new diagnosis of heart failure at any time point, outcomes other than recurrence beyond 6 months, or for hospitalisation and repeat ablation > 3 to 6 months. We assessed the majority of included trials as at low or unclear risk of bias. One trial reported an error in the randomisation process, raising the potential risk of selection bias; most of the included trials were non-blinded; and two trials were at high risk of attrition bias. AUTHORS' CONCLUSIONS: We found evidence to suggest that the use of Class I and/or III antiarrhythmics up to 3 months after ablation is associated with a reduced recurrence of ATa 0 to 6 months after ablation, which may not persist beyond 6 months, and an immediate reduction in hospitalisation for ATa 0 to 3 months after ablation. The evidence suggests there is no difference in rates of all-cause mortality, thromboembolic events, or myocardial infarction between Class I and/or III antiarrhythmics versus control.

Impact of morphine use in acute cardiogenic pulmonary oedema on mortality outcomes: a systematic review and meta-analysis.

BACKGROUND: Morphine is commonly used in the management of acute cardiogenic pulmonary oedema. The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) do not recommend the routine use of opioids in acute heart failure (AHF) due to dose-dependent side effects. However, the effect of morphine remains unclear. Our study aims to investigate the link between morphine use in acute cardiogenic pulmonary oedema and mortality. METHODS: PubMed and Embase databases were searched from inception to October 2021. All studies were included (randomized, non-randomized, observational, prospective and retrospective). The references for all the articles were reviewed for potential articles of interest with no language restrictions. Studies looking at in-hospital mortality along with other outcomes were chosen. The Newcastle-Ottawa scale was used to appraise the studies. Heterogeneity was assessed using I2. Meta-analysis was conducted using the Review Manager Software version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), by computing odds ratios (ORs) for pooled in-hospital mortality and clinical outcomes. RESULTS: Six observational studies out of the 73 publications identified were eligible for the meta-analysis giving a total sample size of 152,859 (mean age 75, males 48%). Of these, four were retrospective analyses. The use of morphine in acute cardiogenic pulmonary oedema was associated with an increased rate of in-hospital mortality [OR = 2.39, confidence interval (CI) = 1.13 to 5.08, p = 0.02], increased need for invasive ventilation (OR = 6.14, CI = 5.84 to 6.46, p < 0.00001), increased need for non-invasive ventilation (OR = 1.85, CI = 1.45 to 2.36, p < 0.00001) and increased need for vasopressors/inotropes (OR = 2.93, CI = 2.20 to 3.89, p < 0.00001). CONCLUSION: Based on the observational studies, morphine use in acute cardiogenic pulmonary oedema is associated with worse outcomes. Further randomized controlled trials are needed to confirm any causative effect of morphine on mortality rates in acute cardiogenic pulmonary oedema.

The Role of SGLT2 Inhibitors in Heart Failure: A Systematic Review and Meta-Analysis.

AIMS: Recent randomised controlled trials (RCTs) have shown a significant prognostic benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the cardiovascular (CV) profile of patients with diabetes. This systematic review and meta-analysis aim to provide a concise evaluation of all the available evidence for the use of these agents in patients with heart failure (HF) regardless of their baseline diabetes status. METHODS AND RESULTS: PubMed, Web of Science, and Cochrane library databases were systematically searched from inception until November 20th 2020. Eight studies consisting of 13,275 patients were included in the meta-analysis. For the total population, SGLT2 inhibitors reduced the risk of all-cause mortality (HR: 0.83; 95% CI: 0.75-0.91; I 2 0%), hospitalisation for HF (HR: 0.68; 95% CI: 0.61-0.75; I 2: 0%), CV death (HR: 0.82; 95% CI: 0.74-0.92; I 2: 0%), and hospitalisation for HF or CV death (HR: 0.72; 95% CI: 0.66-0.78; I 2: 0%). Subgroup analyses of the total population according to the diabetes status showed that SGLT2 inhibitors significantly reduced the risk of hospitalisation for HF (HR: 0.68; 95% CI: 0.61, 0.75; I 2: 0%), as well as the risk of hospitalisation for HF or CV death (HR: 0.72; 95% CI: 0.66, 078; I 2: 0%) and CV death (HR: 0.82; 95% CI: 0.74, 0.91; I 2: 0%). CONCLUSIONS: The results of this meta-analysis confirm the growing evidence in the literature of the favourable profile of SGLT2 inhibitors in cardiovascular outcomes and mortality in patients with heart failure regardless of the baseline diabetes status. This systematic review has been registered with PROSPERO (CRD42021224777).

Biomarkers Associated with Mortality in Aortic Stenosis: A Systematic Review and Meta-Analysis.

The optimal timing of aortic valve replacement (AVR) remains controversial. Several biomarkers reflect the underlying pathophysiological processes in aortic stenosis (AS) and may be of use as mortality predictors. The aim of this systematic review and meta-analysis is to evaluate the blood biomarkers utilised in AS and assess whether they associate with mortality. PubMed and Embase were searched for studies reporting baseline biomarker level and mortality outcomes in patients with AS. A total of 83 studies met the inclusion criteria and were systematically reviewed. Of these, 21 reporting brain natriuretic peptide (BNP), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin and Galectin-3 were meta-analysed. Pooled analysis demonstrated that all-cause mortality was significantly associated with elevated baseline levels of BNP (HR 2.59; 95% CI 1.95-3.44; p < 0.00001), NT-proBNP (HR 1.73; 95% CI 1.45-2.06; p = 0.00001), Troponin (HR 1.65; 95% CI 1.31-2.07; p < 0.0001) and Galectin-3 (HR 1.82; 95% CI 1.27-2.61; p < 0.001) compared to lower baseline biomarker levels. Elevated levels of baseline BNP, NT-proBNP, Troponin and Galectin-3 were associated with increased all-cause mortality in a population of patients with AS. Therefore, a change in biomarker level could be considered to refine optimal timing of intervention. The results of this meta-analysis highlight the importance of biomarkers in risk stratification of AS, regardless of symptom status.

Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis.

Importance: The chronic receipt of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) has been assumed to exacerbate complications associated with COVID-19 and produce worse clinical outcomes. Objective: To conduct an updated and comprehensive systematic review and meta-analysis comparing mortality and severe adverse events (AEs) associated with receipt vs nonreceipt of ACEIs or ARBs among patients with COVID-19. Data Sources: PubMed and Embase databases were systematically searched from December 31, 2019, until September 1, 2020. Study Selection: The meta-analysis included any study design, with the exception of narrative reviews or opinion-based articles, in which COVID-19 was diagnosed through laboratory or radiological test results and in which clinical outcomes (unadjusted or adjusted) associated with COVID-19 were assessed among adult patients (≥18 years) receiving ACEIs or ARBs. Data Extraction and Synthesis: Three authors independently extracted data on mortality and severe AEs associated with COVID-19. Severe AEs were defined as intensive care unit admission or the need for assisted ventilation. For each outcome, a random-effects model was used to compare the odds ratio (OR) between patients receiving ACEIs or ARBs vs those not receiving ACEIs or ARBs. Main Outcomes and Measures: Unadjusted and adjusted ORs for mortality and severe AEs associated with COVID-19. Results: A total of 1788 records from the PubMed and Embase databases were identified; after removal of duplicates, 1664 records were screened, and 71 articles underwent full-text evaluation. Clinical data were pooled from 52 eligible studies (40 cohort studies, 6 case series, 4 case-control studies, 1 randomized clinical trial, and 1 cross-sectional study) enrolling 101 949 total patients, of whom 26 545 (26.0%) were receiving ACEIs or ARBs. When adjusted for covariates, significant reductions in the risk of death (adjusted OR [aOR], 0.57; 95% CI, 0.43-0.76; P < .001) and severe AEs (aOR, 0.68; 95% CI, 0.53-0.88; P < .001) were found. Unadjusted and adjusted analyses of a subgroup of patients with hypertension indicated decreases in the risk of death (unadjusted OR, 0.66 [95% CI, 0.49-0.91]; P = .01; aOR, 0.51 [95% CI, 0.32-0.84]; P = .008) and severe AEs (unadjusted OR, 0.70 [95% CI, 0.54-0.91]; P = .007; aOR, 0.55 [95% CI, 0.36-0.85]; P = .007). Conclusions and Relevance: In this systematic review and meta-analysis, receipt of ACEIs or ARBs was not associated with a higher risk of multivariable-adjusted mortality and severe AEs among patients with COVID-19 who had either hypertension or multiple comorbidities, supporting the recommendations of medical societies. On the contrary, ACEIs and ARBs may be associated with protective benefits, particularly among patients with hypertension. Future randomized clinical trials are warranted to establish causality.

Iron deficiency for prognosis in acute coronary syndrome - A systematic review and meta-analysis.

BACKGROUND: Iron deficiency (ID) is an important predictor of adverse outcomes in patients with heart failure, however it is unclear whether ID also affects prognosis in patients with acute coronary syndrome (ACS). The aim of this systematic review and meta-analysis was to assess the prognostic value of iron deficiency in patients with ACS. METHODS: We searched PubMed, Web of Science, and the Cochrane library and included cohort studies of patients with ACS that were stratified by ID status. There were no restrictions on definition of ACS or ID. Studies were systematically appraised and data extracted by two independent reviewers. Meta-analysis was performed where two or more studies reported on the same pre-determined outcome measure. RESULTS: Seven studies with 2821 participants were identified, reporting a high prevalence of ID in the ACS population. Three studies reported worse long-term outcomes in the ID population, whereas short-term outcomes were heterogeneous across studies. CONCLUSIONS: Patients with ID presenting with ACS may have a worse long-term prognosis but more studies are required for confirmation. A role for ID in prognosis of patients with ACS and as a potentially treatable condition may have implication for the current management of this patient population.

Ventricular-vascular coupling in heart failure with preserved ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a complex disease underlined by impaired ventricular-vascular coupling (VVC). OBJECTIVES: To evaluate the VVC ratio in HFpEF patients at rest and during exercise and compare it to the healthy and heart failure with reduced ejection fraction (HFrEF) controls. METHODS: PubMed and EMBASE databases were searched for trials that matched the inclusion criteria. Random-effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software. RESULTS: A total of 13 trials met the inclusion criteria. Although VVC ratio was comparable between HFpEF and healthy controls at rest, it was significantly lower in HFrEF compared to HFpEF. During exercise, there was a significant decline in VVC ratio in HFpEF (-0.119, 95% CI (-0.183 to -0.055), p<0.001). CONCLUSION: VVC ratio, although 'preserved' at rest in HFpEF patients, was overtly impaired during exercise highlighting the importance of dynamic testing.

Effect of Renin-Angiotensin-Aldosterone System Inhibitors in Patients with COVID-19: a Systematic Review and Meta-analysis of 28,872 Patients.

PURPOSE OF REVIEW: The role of renin-angiotensin-aldosterone system (RAAS) inhibitors, notably angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), in the COVID-19 pandemic has not been fully evaluated. With an increasing number of COVID-19 cases worldwide, it is imperative to better understand the impact of RAAS inhibitors in hypertensive COVID patients. PubMed, Embase and the pre-print database Medrxiv were searched, and studies with data on patients on ACEi/ARB with COVID-19 were included. Random effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software. RECENT FINDINGS: A total of 28,872 patients were included in this meta-analysis. The use of any RAAS inhibition for any conditions showed a trend to lower risk of death/critical events (OR 0.671, CI 0.435 to 1.034, p = 0.071). Within the hypertensive cohort, however, there was a significant lower association with deaths (OR 0.664, CI 0.458 to 0.964, p = 0.031) or the combination of death/critical outcomes (OR 0.670, CI 0.495 to 0.908, p = 0.010). There was no significant association of critical/death outcomes within ACEi vs non-ACEi (OR 1.008, CI 0.822 to 1.235, p = 0.941) and ARB vs non-ARB (OR 0.946, CI 0.735 to 1.218, p = 0.668). This is the largest meta-analysis including critical events and mortality data on patients prescribed ACEi/ARB and found evidence of beneficial effects of chronic ACEi/ARB use especially in hypertensive cohort with COVID-19. As such, we would strongly encourage patients to continue with RAAS inhibitor pharmacotherapy during the COVID-19 pandemic.

The effectiveness of a nationwide interactive ECG teaching workshop for UK medical students.

PURPOSE: Interpreting a twelve­lead electrocardiogram (ECG) is a basic, albeit essential skill for most healthcare professionals to attain. Despite its importance, evidence suggests that the competency of healthcare professionals to interpret ECGs can be improved. We evaluated the effectiveness of a national interactive workshop designed to improve ECG interpretation in the UK medical student cohort. METHODS: UK medical students who attended a national workshop were asked to complete a pre- and post- workshop test which comprised of 20 ECGs which showed a variety of pathologies relating to conduction disturbances, tachycardia and acute coronary syndromes. The workshop was interactive and consisted of 6 h of ECG tutorials, divided into hourly sessions which covered all key topics such as 'basic electrophysiology' and 'electro-conduction problems'. Pre- and post-workshop test scores were compared by difference in means using the paired two-tailed t-test. RESULTS: A total of 145 participants completed the pre-test and of those 44 completed both the pre and post-test. The mean pre-test and post-test scores were 9.7/20 questions (48.9%) and 11.2/20 questions (56.2%) respectively, with a mean improvement of 1.5/20 (7.3%) from pre- to post-test (+7.3%, 95% CI: +1.8 to +12.8%, p = 0.01). CONCLUSION: A national ECG workshop which emphasizes activity-based learning may be effective in improving the competency of medical students to interpret ECGs. Further exploration with multi-center controlled studies involving a diverse cohort of students and analyses to determine their cost-effectiveness is warranted.